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In a recent TED Talk featured on NPR, Nobel Prize-winning biochemist Jennifer Doudna discussed the transformative potential of CRISPR technology in treating complex diseases by targeting the human microbiome—the vast community of bacteria and microbes living in and on our bodies. Doudna, renowned for her co-discovery of the CRISPR-Cas9 gene-editing tool, highlighted how this technology can act like a "scalpel," allowing scientists to edit specific genes within particular microbes without disrupting entire microbial communities. This precision offers promising avenues for noninvasive therapies against conditions such as asthma, Alzheimer's, obesity, and diabetes, all of which have been linked to dysfunctional gut microbiomes.

Doudna emphasized that combining CRISPR with metagenomics—a technique that maps out microbial communities—can create a new field called precision microbiome editing. This approach has significant implications not only for human health but also for environmental sustainability. For instance, modifying the microbiomes of livestock could reduce methane emissions by up to 80%, addressing a significant contributor to climate change. By editing microbiomes at birth, these interventions could have long-lasting effects without ongoing treatments.

Mouse models are instrumental in advancing Doudna's goals of precision microbiome editing. They provide a controlled environment to study the effects of specific genetic modifications on complex biological systems. Using mouse models, researchers can observe how altering particular genes within the microbiome impacts disease development and progression. This accelerates the development of safe and effective CRISPR-based therapies before they are considered for human trials. The insights gained from these models are crucial for translating precision microbiome editing from the laboratory to real-world applications, ultimately helping to build a more resilient future for human health and the planet.

For the full transcript of Jennifer Doudna's talk, visit NPR.

The MiniMUGA genotyping array, a vital tool for genetic quality control in laboratory mice, has been updated to improve its performance. Used in over 40,000 genotyping tests, MiniMUGA helps research programs like the Collaborative Cross (CC) and the Mutant Mouse Resource and Research Centers (MMRRC). The latest updates fix previous limitations and enhance the accuracy of genetic analysis by improving marker annotation, consensus genotypes, and the informatics pipeline.

These updates address key limitations in the original analysis pipeline, increasing the reliability of marker annotation and improving the consensus genotypes for a broader set of inbred strains. Using over 8,500 new samples, the revised pipeline enhances the identification and quantification of specific genetic backgrounds and includes important features such as chromosomal sex determination and construct detection.

Key Improvements

  • Enhanced Marker Annotation: The performance of over 10,800 SNP markers has been re-assessed, leading to better clustering and more accurate genotype calls, reducing errors in background identification and inbreeding estimates.
  • Expanded Detection Capabilities: MiniMUGA now detects two additional genetic constructs, the cHS4 insulator, and the Flippase (Flp) construct, commonly used in laboratory mouse models.
  • Updated Informatics Pipeline: Significant changes to the analysis pipeline include removing arbitrary thresholds, expanding background determination, and incorporating the Y chromosome and mitochondrial genome into the genetic ideogram, providing a more comprehensive report.
  • Improved Consensus Genotypes: The number of inbred strains with consensus genotypes has expanded to 242, with greater representation of biological replicates, ensuring higher accuracy in detecting substrain-specific diagnostic SNPs.
  • User-Friendly Reports: The updated layout simplifies data interpretation. It features a new section summarizing genetic background in table format and a clearer, more comprehensive ideogram that visualizes each sample's genomic makeup.

These updates to the MiniMUGA genotyping array are expected to benefit a wide range of mouse research applications. The improved rigor and reproducibility in genetic analysis will contribute to more reliable research outcomes in genetics, disease mechanisms, and therapeutic development. MiniMUGA’s ability to provide detailed genetic backgrounds and substrain-specific diagnostics makes it a valuable tool for maintaining the integrity of laboratory mouse colonies and supporting global research.

For more information, visit the unlocked article here.


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Welcome to the Mutant Mouse Resource & Research Centers (MMRRC) Website

The MMRRC is the nation’s premier national public repository system for mutant mice. Funded by the NIH continuously since 1999, the MMRRC archives and distributes scientifically valuable spontaneous and induced mutant mouse strains and ES cell lines for use by the biomedical research community. The MMRRC consists of a national network of breeding and distribution repositories and an Informatics Coordination and Service Center located at 4 major academic centers across the nation. The MMRRC is committed to upholding the highest standards of experimental design and quality control to optimize the reproducibility of research studies using mutant mice. The MMRRC is supported by the Office of Research Infrastructure Programs (ORIP) in the Office of the Director at NIH. More than 60,000 mutant alleles are maintained as live mice, cryopreserved germplasm, and/or mutant ES cells. Live mice are supplied from a production colony, from a colony recovered from cryopreservation, or via micro-injection of ES cells. An MMRRC facility may offer cryopreserved material for resuscitation at the recipient scientist's institution.