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In groundbreaking research, scientists have elucidated the effects of neuroinflammation on brain metabolism in Alzheimer's disease using the APPswe/PS1dE9 mouse model (MMRRC Strain # 034829). This study promises to enhance early diagnostic methods and the development of targeted treatments.
Employing in vivo 2-photon microscopy alongside the Oxyphor 2P oxygen sensor, the team measured oxygen levels and capillary blood flow in the brains of mice before and after inducing neuroinflammation with lipopolysaccharide (LPS). Initially, Alzheimer's mice exhibited a lower metabolic demand than healthy counterparts, with similar capillary blood flow across both groups.
After the LPS treatment, both groups showed significant decreases in oxygen levels with increased oxygen extraction, while capillary flow remained stable. These findings suggest that neuroinflammation primarily affects brain metabolism rather than blood flow, underlining its potential as a target for early intervention in Alzheimer's progression.
The implications of this study extend beyond Alzheimer's disease, potentially offering insights into other conditions where neuroinflammation affects cognitive functions. This research underscores the importance of targeting inflammation in early therapeutic strategies and invites further investigation into the complex interactions between neuroinflammation and cerebral energetics.
Paper Source: 10.1186/s13195-024-01444-5 Mouse Model: APPswe/PS1dE9
Groundbreaking research has shed light on the crucial role of growth cones in neuron migration, utilizing various mouse models, including a model supplied by the Mutant Mouse Resource & Research Centers (MMRRC). The dynamic structures of cones, pivotal in navigating the neuronal landscape, demonstrate the intricacies of brain development and repair processes.
The use of MMRRC mice in this study has been instrumental in advancing the understanding of neuronal growth cones and their role in brain development and repair. By exploring the sophisticated mechanisms of neuron migration, this research paves the way for innovative treatments to enhance brain healing and functional recovery, marking a significant milestone in neuroscience.
Publication: Identification of the growth cone as a probe and driver of neuronal migration in the injured brain
Mouse Model Used: STOCK Tg(Dcx-EGFP)BJ224Gsat/Mmmh
NIH-Funded Study at UT Austin Opens New Doors for Neuropathic Pain Treatment with MMRRC Models.
In a significant development, researchers at the University of Texas at Austin, supported by the National Institutes of Health (NIH), have identified a promising new approach to treating neuropathic pain. Highlighted by the NIH's new director, Dr. Monica M. Bertagnolli, the study utilized mice from the Mutant Mouse Resource & Research Centers (MMRRC) and the Knockout Mouse Program (KOMP) to explore innovative treatment methods.
The research focused on a specific molecule capable of binding to a protein closely involved in the mechanisms of neuropathic pain, a condition that affects millions worldwide. This binding has been shown to reduce the hypersensitivity to pain caused by nerve damage, offering a beacon of hope for those suffering from this chronic condition.
Dr. Bertagnolli emphasized the importance of this discovery, noting the critical role of NIH-funded research in advancing medical science and improving patient outcomes. The use of MMRRC mice was pivotal, demonstrating the value of these resources in facilitating high-quality research.
This breakthrough represents a vital step in developing more effective treatments for neuropathic pain, underscoring the significance of collaboration and investment in scientific research.
NIH Director Announcement: https://twitter.com/NIHDirector/status/1757170335361982975
Paper Reference: https://www.pnas.org/doi/10.1073/pnas.2306090120
Mouse Model Used: https://www.mmrrc.org/catalog/sds.php?mmrrc_id=50147
The Mutant Mouse Resource & Research Centers (MMRRC) has again demonstrated its pivotal role in advancing biomedical research. A recent review spanning a decade has highlighted the significant strides made in citation practices for research resources, particularly in the context of transgenic animals and antibodies, with the MMRRC at the forefront of this progress.
Background In biomedical research, resources like transgenic animals and antibodies are essential. Their effective utilization and tracking hinge on the accuracy and consistency of citation practices. Historically, this has been a challenge due to inadequate systems for tracking resource usage, leading to approximately 50% of these resources being not easily findable in academic literature.
The RRID Initiative and MMRRC's Role The Resource Identification Initiative (RRID) has collaborated with journals and resource providers to refine citation practices to address this crucial gap. The MMRRC, a key player in this initiative, has been instrumental in promoting the use of RRIDs (Research Resource Identifiers) among the scientific community.
Key Findings from the Review The review, covering ten years of citation data from five university-based stock centers, revealed:
Impact and Future Outlook This advancement in citation practices, championed by the MMRRC, not only facilitates better tracking and reproducibility of research but also aligns with the National Institutes of Health's (NIH) emphasis on research rigor and transparency. The MMRRC's efforts reflect a broader commitment to enhancing the quality and reliability of biomedical research.
"We are proud to be at the vanguard of this significant change in the research community," said a spokesperson for the MMRRC. "Improving the way we cite and track research resources is not just about better record-keeping; it's about enhancing the integrity and reproducibility of scientific research, which is at the heart of our mission."
For more information, visit https://doi.org/10.1101/2024.01.15.575636.
In the complex and fascinating realm of retinal cell biology, a recent groundbreaking study has illuminated the crucial role of the NFIA gene in the development of retinal cells, specifically focusing on a particular type of cell known as the AII amacrine cell. This cell type is fundamental in the intricate network of the eye, playing a significant role in processing visual information.
Understanding AII Amacrine Cells
AII amacrine cells are specialized neurons in the retina, the light-sensitive layer lining the back of the eye. These cells are indispensable in the visual system, playing a critical role in the processing and interpreting of visual signals. They contribute substantially to our visual acuity and our overall perception of the visual world.
The Crucial Role of the NFIA Gene
Through advanced research utilizing mouse models, particularly those provided by the Mutant Mouse Resource and Research Centers (MMRRC), the NFIA gene has emerged as a pivotal factor in developing AII amacrine cells. Studies indicate that when the NFIA gene is inactive or dysfunctional, there is a marked reduction in the population of these essential retinal cells.
Broad Implications of the Research
The consequences of fewer AII amacrine cells extend beyond a simple reduction in cell count. This deficiency can lead to significant alterations in the overall functionality of the retina, potentially impacting various aspects of eye health. This new understanding is crucial for comprehending various ocular conditions and diseases, opening new possibilities for exploring treatments for retinal disorders originating from cellular development issues.
Advancing Eye Health Research
This research represents a significant leap forward in understanding the complex interplay between genetics and cellular biology in our bodies. Gaining insights into the role of specific genes, such as NFIA, in developing retinal cells is vital for medical science. It holds immense potential for developing treatments for a range of eye diseases.
Future Prospects in Neurodevelopment and Retinal Research
The findings from this study lay the groundwork for further exploration in the vast neurodevelopment and retinal research field. As scientists continue to unravel the complexities of the eye and its cellular makeup, we move closer to groundbreaking advancements that could revolutionize our approach to eye health treatment and understanding. This research adds to our knowledge of the eye and opens doors to potential innovations in medical science, particularly in the realm of ophthalmology and neurobiology.
Find this study here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10711738/
When it comes to stroke recovery, understanding the cellular mechanisms at play is a critical step towards developing effective therapies. A recent groundbreaking study, utilizing mice from the Mutant Mouse Resource and Research Centers (MMRRC), has provided deeper insights into these mechanisms, shedding light on the role of the transcription factor signal transducer and activator of transduction 1 (STAT1) in ischemic stroke recovery.
STAT1 and Stroke: An Evolving Understanding
The connection between STAT1 and ischemic stroke has been established, with STAT1 known to contribute to acute neuronal death within the first 24 hours. However, the impact of STAT1 on brain microglia and macrophages (Mi/MΦ) - cells that can shift to a harmful or advantageous phenotype following a stroke - and its influence on long-term recovery were previously unknown.
To unravel this mystery, researchers turned to MMRRC mice. They generated a model featuring a tamoxifen-induced, Mi/MΦ-specific knockout (mKO) of STAT1, and then induced ischemic stroke via a procedure known as transient middle cerebral artery occlusion (MCAO).
Inflammation and Recovery: The Key Role of STAT1
The study showed that STAT1 was activated in Mi/MΦ three days after MCAO - the subacute stage of stroke. Intriguingly, selective deletion of STAT1 in these cells did not alter neuronal cell death or infarct size within the first 24 hours post-MCAO. Instead, it bolstered the release of high mobility group box 1 and increased the production of arginase 1-producing Mi/MΦ three days after MCAO, suggesting an amplified inflammation-resolving response.
The implications of this for long-term post-stroke recovery were substantial. MMRRC mice with STAT1 mKO exhibited less brain inflammation in the subacute stage post-MCAO and reduced long-term white matter injury. This improved functional recovery for at least five weeks post-MCAO, a benefit seen in both male and female mice.
STAT1: A Promising Target for Therapeutic Intervention
The findings suggest that while Mi/MΦ-targeted STAT1 KO does not offer immediate neuroprotection, it does augment the inflammation-resolving actions of Mi/MΦ, facilitating long-term functional recovery after stroke. This points to STAT1 as a promising therapeutic target for harnessing beneficial Mi/MΦ responses and improving long-term outcomes for ischemic stroke patients.
The use of MMRRC mice in this groundbreaking research provides invaluable insights into post-stroke recovery mechanisms. The results could lead to innovative therapeutic approaches for treating ischemic stroke, making the study a beacon of hope for medical professionals and patients alike.
Source: https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-023-02860-4
In a groundbreaking study, neuroscientists have made significant strides in understanding the relationship between two key areas of the brain, the striatum and the subthalamic nucleus (STN), both integral parts of the basal ganglia system. The study, which was performed on adult male and female mice from the Mutant Mouse Resource & Research Centers (MMRRC), delves into the detailed interaction and organization of the subthalamostriatal projections - direct axonal connections from the STN to the striatum.
To comprehend this complex interplay, the researchers implemented monosynaptic retrograde tracing from specific populations of dorsal striatal neurons. They aimed to quantify the connectivity from STN neurons to various striatal cell types, including spiny projection neurons, GABAergic interneurons, and cholinergic interneurons.
In the study, the team combined ex vivo electrophysiology and optogenetics to decipher the responses of diverse dorsal striatal neuron types to the activation of STN axons. Remarkably, their findings revealed that the connectivity from STN neurons to striatal parvalbumin-expressing interneurons was significantly higher (approximately 4 to 8 times) than that from STN to any of the other striatal cell types examined.
Further, only parvalbumin-expressing interneurons exhibited robust monosynaptic excitatory responses to subthalamostriatal inputs, corroborating the tracing studies' results. The data collectively demonstrate the selectivity of the subthalamostriatal projection for the target cell type, an important finding in neurobiology.
In summary, the study underscores the unique position of glutamatergic STN neurons, highlighting their potential to directly and powerfully influence striatal activity dynamics due to their enriched innervation of GABAergic parvalbumin-expressing interneurons. These findings, generated using mice from the MMRRC, contribute substantially to our understanding of brain dynamics and open new avenues for exploring neurological disorders and potential treatments.
Source: https://www.eneuro.org/content/10/7/ENEURO.0417-21.2023
Neurodevelopmental disorders and SCN2A
Neurodevelopmental disorders (NDD) represent a broad spectrum of conditions disrupting typical neurological growth and development. One gene, SCN2A, has been closely linked to various disorders. Pathogenic variants in SCN2A are monogenic, meaning they originate from alterations in a single gene. However, the phenotypic manifestations of these variants — the observable physical and behavioral traits — show a high degree of variability, often puzzling clinicians and researchers alike. This has led to a comprehensive investigation into the complex genotype-phenotype correlations underlying SCN2A-related NDD.
One way to unravel these complex correlations is to study genetic modifiers. These are genes that can impact the expression of another gene. In the context of rare driver mutations such as those in SCN2A, genetic modifiers can contribute to the considerable variability in disease phenotypes. A standard method to study this is using inbred rodent strains, which exhibit different genetic backgrounds and provide a unique opportunity to observe and analyze the influence of these backgrounds on disease-related phenotypes. Mice used in this research were obtained from the Mutant Mouse Resource & Research Centers (MMRRC), a trusted source for mouse models of human disease.
The recent study developed a mouse model of the SCN2A-p.K1422E variant maintained as an isogenic line on the C57BL/6J (B6) strain. Upon initial characterization, the heterozygous Scn2aK1422E mice showed alterations in anxiety-related behavior and seizure susceptibility, a finding that provided a preliminary view of the phenotypes linked with the SCN2A mutation.
The researchers compared the neurobehavioral assays from mice on the B6 strain with those on a [DBA/2J×B6]F1 hybrid (F1D2) strain to explore how the genetic background could influence these phenotypes. The intriguing results showed that Scn2aK1422E mice displayed lower anxiety-like behavior than their wild-type counterparts. Interestingly, this effect was more pronounced on the B6 background than on the F1D2 background.
They also evaluated strain-dependent differences in seizure activity. Although there were no noticeable differences in the occurrence of rare spontaneous seizures between the two strains, the response to the chemo-convulsant kainic acid did show differences. This difference was not only in seizure generalization but also in the risk of lethality and varied based on both strain and sex of the mice.
The implications of our research are significant. Continued exploration of strain-dependent effects in the Scn2aK1422E mouse model could highlight genetic backgrounds with unique susceptibility profiles. These insights would be precious for future studies, specifically, those focused on identifying specific traits associated with SCN2A-related NDD.
Moreover, by shedding light on the most penetrant phenotypes and potential modifier genes, researchers hope to unearth clues about the primary pathogenic mechanism of the K1422E variant. Such information is paramount for developing novel treatment strategies and personalized medicine approaches for patients with these challenging conditions. In conclusion, by tapping into the potential of mouse models, science can advance understanding of the genetic intricacies of SCN2A-related NDD.
Source: https://via.hypothes.is
Researchers have released the first-ever mouse-specific reference ranges for electrocardiography (ECG) in a monumental advancement for the scientific community. This pioneering work is set to significantly enhance diagnostic decision-making in clinical medicine and our understanding of normality in pre-clinical scientific research involving in vivo models.
This breakthrough is backed by a robust dataset derived from over 26,000 laboratory mice, making it one of the most comprehensive ECG studies involving mice. These data were collected from C57BL/6N wildtype control mice, with the findings stratified by sex and age, adding to the robustness of the developed ECG reference ranges.
What makes this study genuinely groundbreaking are the intriguing findings revealed. The researchers reported minimal sexual dimorphism in heart rate and critical elements from the ECG waveform. This means no significant differences between male and female mice were observed in these parameters.
Furthermore, as expected, anesthesia was shown to induce a decrease in heart rate. This was observed for inhalation (isoflurane) and injectable (tribromoethanol) anesthesia. Such insights will be crucial for experiments where anesthesia is required, allowing researchers to account for these effects in their analysis.
In another important finding, researchers did not observe significant age-related ECG changes in C57BL/6N-inbred mice. The differences in the reference ranges of 12-week-old mice compared to 62-week-old mice were negligible, suggesting that age has a minimal impact on these ECG parameters in this mouse strain.
To test the generalizability of these reference ranges, they were compared with ECG data from a wide range of non-International Mouse Phenotyping Consortium (IMPC) studies. The close overlap in data from a wide variety of mouse strains suggests that these reference ranges have broad applicability and can serve as a robust and comprehensive indicator of normality.
This unique ECG reference resource offers a significant advantage for any experimental study of cardiac function in mice. The ability to compare observed data with robust, mouse-specific ECG reference ranges will significantly enhance the quality and reliability of future cardiac studies. It is a groundbreaking leap in mouse cardiac research with immense potential for future discoveries.
Read the full paper here to dive deeper into these exciting findings.
GABAA receptors (GABAARs) are crucial components of our brain's communication system. They are involved in controlling the activity of neurons, including striatal spiny projection neurons (SPNs). However, the exact role of GABAARs in synaptic integration, particularly in adult SPNs, remains less understood. In a recent study, researchers employed a range of techniques using MMRRC mice to provide new insights into the complex interactions between GABAARs and another type of receptor, ionotropic glutamate receptors (iGluRs), in regulating neuron function.
To explore the role of GABAARs in adult SPNs, the researchers used a combination of molecular, optogenetic, optical, and electrophysiological approaches on ex vivo brain slices from MMRRC mice. Computational tools were also employed to model somatodendritic synaptic integration, which is the process by which neurons combine multiple signals.
The study found that activating GABAARs caused currents with a reversal potential near -60 mV in both juvenile and adult SPNs. Interestingly, this relatively positive reversal potential was not attributed to the expression of a particular protein (NKCC1), but rather to a balance between two other transporters (KCC2 and Cl-/HCO3-cotransporters).
When researchers activated GABAergic synapses, they observed that SPNs became depolarized from their resting down-state. This GABAAR-mediated depolarization worked together with the stimulation of ionotropic glutamate receptors (iGluRs), leading to increased somatic depolarization and dendritic spikes.
Simulations revealed that a diffuse dendritic GABAergic input to SPNs effectively enhanced the response to coincident glutamatergic input. This finding suggests that GABAARs and iGluRs can work in concert to excite adult SPNs when they are in a resting down-state. The inhibitory role of GABAARs appears to be limited to brief periods near the spike threshold.
The results of this study call for a reevaluation of the role of GABAARs in intrastriatal GABAergic circuits. The discovery that GABAARs can work in conjunction with iGluRs to excite adult SPNs in their resting down-state suggests a more complex role in regulating neuron function than previously thought.
By using MMRRC mice and a variety of techniques, the researchers have provided valuable insights into the intricate interactions between GABAARs and iGluRs in adult brain neurons. This knowledge could potentially lead to a better understanding of various neurological disorders and contribute to the development of more effective treatments.
The study using MMRRC mice has shed light on the complex role of GABAARs in adult striatal spiny projection neurons. By demonstrating that GABAARs can work together with iGluRs to excite adult SPNs in their resting down-state, researchers have opened up new avenues for understanding the regulation of neuronal function and the potential implications for neurological disorders.
Source: https://www.biorxiv.org/content/10.1101/2023.03.14.532627v2
Imagine the genome as a city with different neighborhoods, each having its function. Topologically associating domain (TAD) boundaries are like the fences that separate these neighborhoods, maintaining distinct regulatory territories. Disruption of these boundaries may interfere with regular gene expression and cause diseases, but the full impact remains unclear.
Researchers utilized CRISPR genome editing in mice to investigate the consequences of deleting eight TAD boundaries. All deletions led to noticeable molecular or organismal phenotypes, including chromatin interaction or gene expression changes, reduced viability, and anatomical abnormalities.
In 88% of cases, local 3D chromatin architecture was altered. This included merging TADs and changed contact frequencies within adjacent TADs. Additionally, 63% of the examined loci exhibited increased embryonic lethality or developmental issues. For instance, a TAD boundary deletion near Smad3/Smad6 led to complete embryonic lethality, while another near Tbx5/Lhx5 caused severe lung malformation.
This study highlights the importance of TAD boundary sequences for proper genome function and organism development. It also emphasizes the need to consider the potential pathogenicity of noncoding deletions affecting TAD boundaries in clinical genetics screening. By understanding the impact of TAD boundary disruptions, we can better diagnose and potentially treat genetic disorders.
Source: https://www.nature.com/articles/s42003-023-04819-w#Sec8
Heart failure affects millions worldwide. Recently, a groundbreaking study has revealed the relationship between three molecules—MIAT, miR-150, and Hoxa4—which could hold the key to new treatment strategies for heart failure patients.
Researchers used genetically modified mice from the Mutant Mouse Resource & Research Center (MMRRC) to investigate the roles of MIAT, miR-150, and a novel target, Hoxa4, in heart failure. The mice were subjected to a model of myocardial infarction and various tests to evaluate their cardiac function and molecular mechanisms.
The study found that increasing MIAT levels worsened cardiac damage while deleting MIAT protected the mice's hearts. Importantly, increasing miR-150 levels helped counteract MIAT's harmful effects. The scientists also identified Hoxa4 as a new downstream target of the MIAT/miR-150 pathway and discovered that mice lacking Hoxa4 exhibited protection from myocardial infarction.
This research unveiled a crucial interaction among MIAT, miR-150, and Hoxa4, providing valuable insights into a novel regulatory mechanism involved in heart failure. Understanding these molecular connections could pave the way for new treatments targeting these molecules, offering hope to heart failure patients worldwide. The study also highlights the importance of using genetically modified mice in advancing our knowledge of complex diseases like heart failure.
https://www.ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.121.008686
The search for new treatments and cures for rare diseases is an ongoing challenge for researchers worldwide
One of the key strategies in this effort is the identification of genes that may be implicated in these diseases, particularly those involved in ciliopathies - a group of rare genetic disorders caused by defects in the function or structure of cilia.
At the MMRRC, we constantly explore innovative ways to advance medical research and improve patient outcomes. A recent study used the International Mouse Phenotyping Consortium (IMPC) database of single-gene knockout (KO) mice to identify candidate ciliopathy genes. These mice are found and available from the MMRRC.
The approach involved screening mouse lines with ocular, renal, or reproductive trait abnormalities for phenotypes. Then, the STRING protein interaction tool was used to identify interactions between known cilia gene products and those encoded by the genes in individual knockout mouse strains. This allowed generation of a list of "candidate ciliopathy genes" - 32 genes encoded proteins that were predicted to interact with known ciliopathy proteins. Of these, 25 had no previously described roles in ciliary pathobiology.
To provide evidence of the potential clinical relevance of these candidate genes, histological and morphological data was presented from knockout mouse lines with phenotypes resembling those found in ciliopathies. These included genes such as Abi2, Wdr62, Ap4e1, Dync1li1, and Prkab1.
The study demonstrates the power of the IMPC phenotype data for mechanistic studies, target discovery, rare disease diagnosis, and preclinical therapeutic development trials. By uncovering genes with no previously known role in ciliary biology, new avenues for research and potential treatments for ciliopathies are open for discovery.
At the MMRRC, we are committed to advancing medical research and improving patient outcomes. Our study is just one example of the innovative research being conducted in our labs every day. Stay tuned for more exciting developments in the search for new treatments and cures for rare diseases.
https://doi.org/10.1038/s41598-022-19710-7
Higgins, K., Moore, B.A., Berberovic, Z. et al. Analysis of genome-wide knockout mouse database identifies candidate ciliopathy genes. Sci Rep 12, 20791 (2022).
Mutant mouse genetic modifications have revolutionized biomedical research, enabling scientists to study specific gene mutations and their effects on biological processes. This study used data mining to investigate congenital abnormalities underlying the Microphthalmia, Anophthalmia, and Coloboma (MAC) spectrum disease, a group of eye malformations that cause childhood visual impairment.
The research involved a systematic forward screening of the mammalian genome, using the International Mouse Phenotyping Consortium (IMPC) database to identify knockout lines with genetically associated eye defects in mouse embryos. The IMPC database is a valuable resource for researchers, as it contains a vast array of information on knockout mouse models and associated phenotypes.
Data mining efforts identified 74 unique knockout lines (genes) with ocular abnormalities, most of which were small or absent eyes - findings most relevant to MAC spectrum disease in humans. Of these 74 lines, 27 had previously published knockout mouse models, of which only 15 had ocular defects identified in the original publications. This left 12 previously published gene knockouts with no reported ocular abnormalities and 47 unpublished knockouts with ocular abnormalities identified by the IMPC. These represented 59 genes not previously associated with early eye development in mice.
Further analysis identified 19 of these genes with a reported human eye phenotype, demonstrating the clinical relevance of our findings. In total, 40 previously unimplicated genes linked to mammalian eye development were identified, highlighting the power of mutant mouse genetic modifications in identifying novel gene targets for rare diseases.
Bioinformatic analysis showed that several of the IMPC genes colocalized to several protein anabolic and pluripotency pathways in early eye development. Notably, analysis suggests that the serine-glycine pathway producing glycine, a mitochondrial one-carbon donator to folate one-carbon metabolism (FOCM), is essential for eye formation.
The findings provide a valuable resource for researchers investigating the genetic abnormalities underlying MAC spectrum disease and other congenital blinding diseases. Using data mining and mutant mouse genetic modifications, novel genes and pathways required for early eye development are open for further research application. These findings can potentially accelerate the diagnosis and treatment of these rare diseases.
https://doi.org/10.1186/s12915-022-01475-0
Chee, J.M., Lanoue, L., Clary, D. et al. Genome-wide screening reveals the genetic basis of mammalian embryonic eye development. BMC Biol 21, 22 (2023).
The Mutant Mouse Resource and Research Center (MMRRC), the official National Institute of Health (NIH) repository of mouse models, is pleased to announce the availability of the Collaborative Cross mouse population for distribution. The Collaborative Cross (CC) is a multi-parental genetic reference mouse population derived from eight founder inbred strains, encompassing an extraordinary level of genetic diversity. The CC is an ideal population for studying complex traits and for identifying novel models of disease in the context of natural genetic variation.
This newly acquired collection has been deposited into the MMRRC at UNC. These strains have been available through the Systems Genetics Core Facility (SGCF) at UNC since 2012. The breeding of the CC lines started with 8 inbred founders obtained from the Jackson Laboratory. Breeding was performed at Oak Ridge National Laboratory in Tennessee, International Livestock Research Institute (ILRI) in Kenya, Geniad, Ltd in Western Australia, and the Jackson Laboratory.
The CC collection is composed of 63 strains. Each CC strain has deep and uniform genetic characterization including MiniMUGA consensus genotypes, haplotype mosaics, and whole genome sequences. All but 8 strains are >95% inbred as of 2020 (range 88-100%). The CC strains are listed on the MMRRC’s website (here).
Experimental cohorts and breeding pairs/trios are available. The CC collection is maintained as repository live (i.e., continuously bred). Note that breeding productivity and order queues can affect fulfillment dates, and the MMRRC may recommend delivery of orders in batches. For ordering inquiries, please contact MMRRC_CC@unc.edu.
We are the pre-eminent public national mutant mouse repository and distribution archive in the USA, serving as a national resource of mutant mice available to the global scientific community for biomedical research..
https://link.springer.com/article/10.1007/s00335-021-09894-0
COVID-19 is a serious public health threat and researchers around the globe are turning to mouse models as a critical tool in viral pathogenesis, vaccine, and drug treatment discovery research. To help support these efforts, the MMRRC is distributing several COVID-19 related mouse models. To learn more about the COVID-19 related list of available strains available from the MMRRC, please visit: https://www.mmrrc.org/catalog/covid_models.php
The MMRRC is now maintaining two exciting new lines with broad applicability and interest to scientists working in many different areas. These mouse lines are called “Mouse for Actively Recording Cells 1” or MARC1. Donated by Dr. George M. Church, Ph.D., and Dr. Reza Kalhor, Ph.D., of Harvard Medical School, they are used for barcoding and lineage tracing applications in the mouse (PMID:30093604). Although these lines do not express any disease-related phenotypes, when a MARC1 mouse is crossed to mice expressing cas9 (universally or in a lineage-specific manner), combinatorial and cumulative barcoding starts in the progeny during their development, leading to developmentally barcoded animals that can be used for a multitude of applications, including lineage tracing.
The available lines are:
Please contact our customer service center at service@mmrrc.org if you have any questions about these new lines.
This March during Brain Injury Awareness Month, the NIH is conducting a campaign that is aimed at educating the general public about the incidence of brain injuries and the needs of people with brain injuries. For more information on traumatic brain injuries, visit the NIH’s official website:
https://www.ninds.nih.gov/Disorders/All-Disorders/Traumatic-Brain-Injury-Information-Page
Popular MMRRC Brain Injury Awareness Month Strains:
Contact us if you need assistance with learning more about strains related to Breast Cancer in the MMRRC repository.
This February during American Heart Month, the NIH is encouraging people to take charge of their health and start new, heart-healthy behavior that can help reduce their risk of heart disease and stroke. For more information, visit the NIH’s official website:
https://www.nhlbi.nih.gov/health/educational/hearttruth/lower-risk/what-is-heart-disease.htm
Popular MMRRC Heart Month Strains:
This month seeks to promote health and awareness of birth defects. At the MMRRC, we understand that data sharing is essential to speed translation of research results into knowledge, therapies, and procedures to improve human health. The MMRRC is committed to sharing data and offers several strains and models to advance research in structural birth defects and foster discovery of shared genetic pathways between disorders:
https://www.nichd.nih.gov/about/overview/directors_corner/prev_updates/010715-birth-defects
Popular research models available in the MMRRC include:
Contact us if you need assistance with learning more about strains related to birth defects in the MMRRC repository.
The MMRRC is pleased to welcome its newest collection of cell lines to the repository. The UC Davis/NIH NeuroMab Facility has deposited 473 Hybridoma Cell Lines into the MMRRC at UC Davis.
Hybridoma cell lines are immortal monoclonal antibody producing cells that can be grown in tissue culture at any scale to produce monoclonal antibodies. Each of the 473 cell lines in the MMRRC produced monoclonal antibodies validated for the specificity and efficacy in brain research applications at UC Davis/NIH NeuroMab Facility.
This new collection will empower researchers with the ability to produce large quantities of specific and highly validated monoclonal antibodies at low cost. One of the other benefits of having this collection in the MMRRC is that scientists also have access to knockout mouse lines for genes that encode protein targets of the NeuroMAb monoclonal antibodies. Accessibility of these cell lines will allow investigators to explore the dynamic organization of specific cell antibodies critical to understanding and improving health and disease.
Check out the new collection here
This October during Breast Cancer Awareness Month, the NIH is joining efforts across the U.S. to raise awareness, share information, and highlight research to help fight the disease. For more information on Breast Cancer, visit the NIH’s official website:
https://www.cancer.gov/
Popular MMRRC Breast Cancer Awareness Month Strains:
This September during Prostate Cancer Awareness Month, the NIH is working to provide easily accessible prostate health screenings and to educate the public about risk factors of prostate related diseases. For more information on Prostate Cancer, visit the NIH’s official website:
https://report.nih.gov/nihfactsheets/ViewFactSheet.aspx?csid=60
Popular MMRRC Prostate Cancer Awareness Month Strains:
Contact us if you need assistance with learning more about strains related to Prostate Cancer in the MMRRC repository.
Come learn from leading scientific researchers about the latest developments and research surrounding Precision Mouse Modeling as it translates to Human Disease. Sponsored by the NIH, ORIP, this information symposium will be held from 1:30pm – 5pm on September 11 at Monsanto Auditorium of the Bond Life Science Center on the University of Missouri-Columbia.
MMRRC Symposium Flyer
This August during Spinal Muscular Atrophy Awareness Month, the NIH is raising a public health campaign to spread awareness of spinal muscular atrophy and the availability of carrier screening. For more information on Spinal Muscular Atrophy, visit the NIH’s official website:
https://www.ninds.nih.gov/Disorders/All-Disorders/Spinal-Muscular-Atrophy-Information-Page
Popular MMRRC Spinal Muscular Atrophy Awareness Month Strains:
Contact us if you need assistance with learning more about strains related to Spinal Muscular Atrophy in the MMRRC repository.
June is Alzheimer’s Awareness Month, and a popular research area for MMRRC strains to study the disease. For more information on Alzheimer’s disease, visit the NIH’s official website:
https://www.nia.nih.gov/health/alzheimers
Popular MMRRC Alzheimer’s Awareness Month Strains:
Contact us if you need assistance with learning more about strains related to Alzheimer in the MMRRC repository.
This May during Cystic Fibrosis Awareness Month, the NIH is encouraging the public to support their mission to cure Cystic Fibrosis by participating in walks and sharing facts about the disease on social media. For more information on Cystic Fibrosis, visit the NIH’s official website:
https://ghr.nlm.nih.gov/condition/cystic-fibrosis
Popular MMRRC Cystic Fibrosis Awareness Month Strains:
Contact us if you need assistance with learning more about strains related to Cystic Fibrosis in the MMRRC repository.
This April during Parkinson’s Awareness Month, the NIH is conducting a campaign to gain support for the one million Americans affected by Parkinson’s disease. For more information on Parkinson’s disease, visit the NIH’s official website:
https://www.ninds.nih.gov/Disorders/All-Disorders/Parkinsons-Disease-Information-Page
Popular MMRRC Parkinson’s Awareness Month Strains:
Contact us if you need assistance with learning more about strains related to Parkinson’s disease in the MMRRC repository.
This March during National Kidney Month, he NIH-NIDDK is focusing on raising that Chronic Kidney Disease is a serious condition affecting more than 30 million adults in the United States, yet people in the early stages may not have symptoms. Many people don’t find out they have kidney disease until their kidneys are permanently damaged. To learn more about Kidney Disease, visit the NIH-NIDDK’s official website:
https://www.niddk.nih.gov/health-information/kidney-disease
Popular MMRRC Kidney Disease Month Strains:
Contact us if you need assistance with learning more about the more than 320 strains related to Kidney Disease available in the MMRRC repository.
The Mutant Mouse Resource and Research Center (MMRRC), the official National Institute of Health (NIH) repository of mouse models, is pleased to announce the availability of genetically-altered mice and embryonic stem (ES) cells made as part of the NIH Knockout Mouse Project (KOMP) and previously maintained in the KOMP Repository. The KOMP Repository collection will provide investigators with the convenience of a one-stop portal to one of the largest inventories of mutant mouse strains and ES cell lines available to the biomedical research community.
These newly acquired mouse and ES cell lines have been deposited into the MMRRC at UC Davis. The MMRRC at UC Davis is the largest of four regional archive and distribution centers in the NIH consortium. The MMRRC functions as a single repository resource and is comprised of an Informatics, Coordination and Service Center (ICSC) and three additional regional distribution facilities which include: The Jackson Laboratory, University of Missouri, and University of North Carolina, Chapel Hill. The newly available KOMP Repository mice (4,175 unique lines) & ES cell lines (14,013 unique mutant lines and 7 parental lines) can be accessed by visiting the MMRRC website (www.mmrrc.org) and typing in "KOMP Repository" in the search function, or by using the advanced search function and indicating “Major Collection = KOMP", and then searching by gene of interest, which will allow filtering for ES cells or mice.
The MMRRC was created in 1999, and is supported through the NIH, Office of Infrastructure and Research Programs (ORIP), as the nation’s premier mouse archive and distribution repository. Since that time, the MMRRC has earned an international reputation for the management, cryopreservation, and distribution of scientifically valuable, genetically engineered mouse strains and mouse ES cells. In partnership with researchers around the globe, the MMRRC continues to expand its holdings of mouse models. Today, with more than 59,000 available models, the MMRRC serves as a valuable resource to drive research discoveries for human disease.
This February during American Heart Month, the NIH is encouraging people to take charge of their health and start new, heart-healthy behavior that can help reduce their risk of heart disease and stroke. For more information, visit the NIH’s official website.
Contact us if you need assistance with learning more about strains related to heart disease in the MMRRC repository.
This month seeks to promote health and awareness of birth defects. At the MMRRC, we understand that data sharing is essential to speed translation of research results into knowledge, therapies, and procedures to improve human health. The MMRRC is committed to sharing data and offers several strains and models to advance research in structural birth defects and foster discovery of shared genetic pathways between disorders.
The MMRRC education booth is back from two exciting end of the year conferences in San Diego: ASHG and SfN. Both conferences boasted strong attendance rates, with ASHG claiming their highest attendee count to date. There were many great poster sessions showcasing the latest research efforts involving the use of mouse models. We had the pleasure of meeting many new investigators and students and learning about their research efforts involving the use of mice. We were also excited to provide information about role that the MMRRC plays with archiving and distribution of mouse models, and the importance of rigor and reproducibility. It’s always great to see that our outreach and education efforts can have an impact on increasing awareness of the MMRRC.
#mousemodels #mouseresearch #rigorandreproducibility #NIHORIP #mouseresearchstudies #MMRRC #MMRRCMice #ASHG #ASHG2018 #ASHG18 #SFN2018 #SfN18
This November during Diabetes Awareness Month, the NIH is encouraging people to gain understanding and offer support to those dealing with the challenges of diabetes. For more information on Diabetes, visit the NIH’s official website.
https://www.nih.gov/about-nih/what-we-do/nih-turning-discovery-into-health/diabetes
Popular MMRRC Diabetes Awareness Month Strains:
Contact us if you need assistance with learning more about strains related to Diabetes in the MMRRC repository.
This October during Breast Cancer Awareness Month, the NIH is joining efforts across the U.S. to raise awareness, share information, and highlight research to help fight the disease. For more information on Breast Cancer, visit the NIH’s official website.
Popular MMRRC Breast Cancer Awareness Month Strains
This September during Prostate Cancer Awareness Month, the NIH is working to provide easily accessible prostate health screenings and to educate the public about risk factors of prostate related diseases. For more information on Prostate Cancer, visit the NIH’s official website.
Popular MMRRC Prostate Cancer Awareness Month Strains
This August during Spinal Muscular Atrophy Awareness Month, the NIH is raising a public health campaign to spread awareness of spinal muscular atrophy and the availability of carrier screening. For more information on Spinal Muscular Atrophy, visit the NIH’s official website.
Popular MMRRC Spinal Muscular Atrophy Awareness Month Strains
On July 28th, during World Hepatitis Day, the NIH aspires to join people together and raise the profile of viral hepatitis among the public, the world’s media, and on the global health agenda. For more information on Hepatitis, visit the NIH’s official website.
https://www.niaid.nih.gov/diseases-conditions/hepatitis
Popular MMRRC World Hepatitis Day Strains
Contact us if you need assistance with learning more about strains related to Hepatitis in the MMRRC repository.
This June during Alzheimer’s Awareness Month, the NIH is encouraging people to learn more about Alzheimer’s, share their stories, and take action to fight the disease. For more information on Alzheimer’s disease, visit the NIH’s official website.
Popular MMRRC Alzheimer’s Awareness Month Strains
This May during Cystic Fibrosis Awareness Month, the NIH is encouraging the public to support their mission to cure Cystic Fibrosis by participating in walks and sharing facts about the disease on social media. For more information on Cystic Fibrosis, visit the NIH’s official website.
Popular MMRRC Cystic Fibrosis Awareness Month Strains
The MMRRC is excited to announce the upcoming release of our newly redesigned submission form set for debut on Wednesday, May 2nd 2018.
Along with user-friendly navigation the form has been significantly reduced to only include the bare minimum criteria needed for strain acceptance. The new design allows users to navigate through the submission form easily and effectively with informative tool-tips to help explain and clarify questions.
Our new shorter form will reduce completion time significantly and make multiple submissions a much simpler process. We anticipate a smooth transition over and look forward to hearing your feedback!
This April during Parkinson’s Awareness Month, the NIH is conducting a campaign to gain support for the one million Americans affected by Parkinson’s disease. For more information on Parkinson’s disease, visit the NIH’s official website.
Popular MMRRC Parkinson’s Awareness Month Strains
This March during Brain Injury Awareness Month, the NIH is conducting a campaign that is aimed at educating the general public about the incidence of brain injuries and the needs of people with brain injuries. For more information on traumatic brain injuries, visit the NIH’s official website.
Contact us if you need assistance with learning more about strains related to brain injuries in the MMRRC repository.
https://www.nhlbi.nih.gov/health/educational/hearttruth/lower-risk/what-is-heart-disease.htm.
Representatives from the MMRRC will be attending American Society of Human Genetics 2017 October 17 – 21 in Orlando FL. Please be sure to stop by our education and outreach booth and learn more about how the MMRRC can help you with your mouse related research needs.
http://www.ashg.org/2017meeting/
Representatives from the MMRRC will be attending Society for Neuroscience 2017 November 11 – 15 in Washington, DC. Please be sure to stop by our education and outreach booth and learn more about how the MMRRC can help you with your mouse related research needs.
https://www.sfn.org/annual-meeting/neuroscience-2017
Representatives from the MMRRC will be attending Experimental Biology 2017 April 22 – 26 in Chicago, IL. Please be sure to stop by booth #1412 and learn more about how the MMRRC can help you with your mouse related research needs.
http://experimentalbiology.org/2017/Home.aspx
The IMPC is creating knockout mouse lines for every single protein coding gene in the mouse genome, and characterizing them through standardized, quality-controlled phenotyping tests.
IMPC Flyer
Since 2006, researchers around the world have been working together to generate a targeted knockout mutation for every gene in the mouse genome. The US component of this effort, The Knockout Mouse Project (KOMP), has been providing critical tools for understanding gene function and the genetic causes of human diseases.
In 2016, the National Institutes of Health funded the next phase in the KOMP project called KOMP2 Phase 2 with the objective to produce and phenotype more than 3000 new knockout mouse lines on a C57BL6/N genetic background. Here at the MMRRC, we are pleased to announce that these KOMP2 Phase2 mouse lines will all be made available from the MMRRC repositories. New mouse lines will be added monthly and full phenotyping data will be available.
Genetically engineered mice serve as valuable models of human disease, contributing to major medical breakthroughs. Often, biomedical researchers must develop unique genetically modified strains of mice for experimentation, a costly and time-consuming process. Now, more researchers in fields from immunology to cancer may be able to save time and money by acquiring genetic material from a repository of previously engineered strains.
https://www.niaid.nih.gov/news-events/niaid-supported-research-expands-number-publicly-available-mouse-mutations
Representatives from the MMRRC will be attending The Allied Genetics Conference July 13 – 17 in Orlando FL. Please be sure to stop by our booth and learn more about how the MMRRC can help you with your mouse related research needs. http://www.genetics2016.org
Representatives from the MMRRC will be attending Society for Neuroscience 2016 November 13 –16 in San Diego, CA. Please be sure to stop by booth #4322 and learn more about how the MMRRC can help you with your mouse related research needs. https://www.sfn.org/annual-meeting/neuroscience-2016
Representatives from the MMRRC will be attending Experimental Biology 2016 April 2 – 6 in San Diego CA. Please be sure to stop by booth #1104 and learn more about how the MMRRC can help you with your mouse related research needs. http://experimentalbiology.org/2016/Home.aspx
Representatives from the MMRRC will be attending American Society for Human Genetics 2016 October 18 – 22 in Vancouver, BC. Please be sure to stop by booth #422B and learn more about how the MMRRC can help you with your mouse related research needs. http://www.ashg.org/2016meeting/
Read the recently published article in Nature about how the MMRRC repository provides scientific value and utility through curation, preservation, genetic quality control, and protection from pathogens. Learn about the efforts that the MMRRC takes to help researchers reduce model redundancy and improve reproducibility of studies. http://www.nature.com/news/reproducibility-use-mouse-biobanks-or-lose-them-1.17707
Representatives from the MMRRC will be attending the 66th Annual AALAS National Meeting November 1-5, 2015 Phoenix, AZ. Please be sure to stop by booth #215 and learn more about how the MMRRC can help you with your mouse related research needs. https://www.aalas.org/national-meeting#.VRrfaE10y70
Representatives of the Mutant Mouse Regional Resource Center will be attending the American Society of Cell Biology Meeting in Philadelphia December 6-10. Please come by booth #916 and let us help you with your mouse research needs.
The NIDDK Information Network (dkNET) serves the needs of basic and clinical investigators by providing seamless access to large pools of data relevant to the mission of The National Institute of Diabetes Digestive and Kidney Diseases (NIDDK). The dkNET portal contains information about research resources such as antibodies, vectors and mouse strains, data, protocols, and literature.
The MMRRC is pleased to officially announce the release of our newly redesigned order process! Along with user-friendly navigation and the new "Favorites" feature, the order form has been updated with the latest information and a fresh new look. The new design allows users to navigate through the order process easily and effectively with alerts for missed questions, in-line hints, and the ability to alter contact information within the form. The new Favorites feature allows users to save and organize their favorite products and even allows them to send their favorites list to their registered email account for later reference.
April 26 – 30 Experimental Biology Booth 1439 San Diego, CA, San Diego Convention Center http://experimentalbiology.org/2014/Home.aspx October 18 - 22 American Society Human Genetics Booth TBD San Diego, CA, San Diego Convention Center http://www.ashg.org/2014meeting November 15 – 19 Neuroscience Booth TBD Washington, DC, Walter E. Washington Convention Center http://www.sfn.org/annual-meeting/neuroscience-2014 December 6 - 10 American Society Cell Biology Booth TBD Pennsylvania, PA, Pennsylvania Convention Center http://www.ascb.org/meetings-home
The Mutant Mouse Regional Resource Center (MMRRC) will be attending the 2013 American Society for Cell Biology Meeting December 14 through 18 in New Orleans. The MMRRC has been able to map 900 MeSH terms from attendee publications to mouse models within our repositories. If you are attending the meeting, then please consider visiting our booth and speaking directly with one of our knowledgeable customer service staff members.
The Mutant Mouse Regional Resource Center (MMRRC) repository simple and advanced search methods now include the ability to search by associated Major Medical Subject Heading (MeSH) terms. MeSH is the National Library of Medicine\'s controlled vocabulary thesaurus. It consists of sets of terms naming descriptors in a hierarchical structure that permits searching at various levels of specificity. Major MeSH terms are defined by authors of primary research articles as having the most relevance to the research represented by the article.
The Mutant Mouse Regional Resource Center (MMRRC) will be attending the Society of Neuroscience Meeting in San Diego November 9-13 (booth 3831). Among the thousands of model systems within the MMRRC repository, the MMRRC has 440 neuroscience models in 700 major Medical Subject Heading (MeSH) categories. If you are attending the meeting, then please consider visiting our booth (#3831) and speaking directly with one of our knowledgeable customer service staff members.
The International Mouse Phenotyping Consortium is conducting a survey with the goal of exploring ways to ensure that researchers utilize high-impact mouse-model resources. The on line survey is available here.
When expressed in mice, high levels of Neuregulin 1 (Nrg1) lead to behavioral deficits and hypofunction of glutamatergic and GABAergic pathways similar to that found in human patients with schizophrenia. Don-Yin Min, et al. found that these effects are diminished when Nrg1 levels are returned to normal.The MMRRC has related mouse models.
Evidence that that miR-146a is a downstream-mediator of 16K PRL that could potentially serve as a biomarker and therapeutic target for PPCM.Full publiceation here.The MMRRC has a related ES cell line.
Researchers at UT Southwestern Medical Center have identified a specific gene, Meis1 that regulates the heart’s ability to regenerate after injuries. The original article can be found in Nature.The MMRRC has a GENSAT mouse containing multiple copies of a modified BAC in which EGFP reporter gene is inserted immediately upstream of the Meis1 coding sequence of the targeted gene.
In 2012, the MMRRC was able to successfully deliver 246 out of 247 resuscitation orders. Please consider our services to best meet your research needs.
Scientists Make Mouse Model of Human Cancer, Demonstrate CureUT Southwestern Medical Center scientists report the first successful blocking of tumor development in a genetic mouse model of an incurable human cancer. Blocking the activity of a receptor molecule named CXCR4 inhibited tumor development of malignant peripheral nerve sheath tumors (MPNSTs).
STOCK Tg(Cxcr4-EGFP)CD73Gsat/Mmucd is available from the MMRRC and contains multiple copies of a modified BAC in which EGFP reporter gene is inserted immediately upstream of the coding sequence of the targeted gene.
In an effort to determine MMRRC's contribution to biomedical research, we reached out to all our previous customers and asked for additional information on previous orders. Customers who filled out the raffle form with valid NIH Grant entries and/or Pubmed publication IDs were entered into a raffle with a chance to win a new iPod. The raffle winner was selected today. Congratulations to Dr. Caius G. Radu from University of California, Los Angeles for winning the iPod. We would like to thank all those who participated in this raffle and provided valuable information about their past purchases from MMRRC. We appreciate their time and effort.
Brain diseases associated with the misformed protein tau, including Alzheimers disease and frontotemporal lobar degeneration with tau pathologies, are characterized by neurofibrillary tangles (NFTs) comprised of pathological tau filaments. article Mapt at MMRRC
Our very own Terry R. Magnuson, Ph.D., Sarah Graham Kenan Professor and chair, department of genetics, and vice dean for research, School of Medicine, University of North Carolina, Chapel Hill, and Project Director for the MMRRC at North Carolina-Chapel Hill, was just elected to the Institute of Medicine of the National Academies.
Welcome to the newly revised MMRRC website! The goal of this revision is to modernize the look and feel of MMRRC's web presence. We hope the new simplified search feature will make finding the products you are looking for easier. For any questions/problems you have regarding this release, please email us at service@mmrrc.org, or use the Feedback function to the right side of the page.