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For the 15q13.3 deletion (MMRRC:68235) and duplication (MMRRC:68236), the deleted or duplicated genes are:
A similar mouse model, Df[h15q13]]/+ has been described by researchers from the company Lundbeck (PMID:24090792), displaying increased neuronal excitability in acute seizure assays with increased propensity to develop myoclonic and absence-like seizures but decrease the propensity for clonic and tonic seizures, impaired long-term spatial reference memory and decreased theta frequency in the hippocampus and prefrontal cortex, and decreased amplitudes of auditory evoked potentials. These mice also showed prefrontal neurophysiological dysfunctions and attentional impairment (PMID:26983414), deficits in neuronal spike firing matching clinical neurophysiological biomarkers seen in schizophrenia (PMID:27364459), increase in the vulnerability to the detrimental effect of peripubertal stress exposure (PMID:30188511), a transcriptomic network implicating neuronal energetic abnormalities (PMID:31705054), deficits in spatial learning in the Barnes maze (PMID:32712126), and a loss of astrocytes and synaptic-related changes of the excitatory and inhibitory circuits in the medial prefrontal cortex (PMID:33123721). An acetylcholine7 positive allosteric modulator rescued a schizophrenia-associated brain endophenotype (PMID:27061851). Homozygous mice displayed epilepsy-, autism- and schizophrenia-related phenotypes (PMID:27459725). Another similar 15q13.3 mouse model was developed by scientists from the company Astella Pharma (PMID:26658876). For these mice, macrocephaly, enlarged ventricles, decreased social interactions, increased repetitive grooming behavior, reduced ultrasonic vocalizations, decreased auditory-evoked gamma-band EEG, reduced event-related potentials, and no signs of epilepsy/seizures were reported.
Donor Note: Copy number variations in the 1q21.1 and 15q13.3 regions have been linked to neurodevelopmental disorders like schizophrenia and autism at a genome-wide level (PMID:26130694).
The donor constructed mice with a 1.4-Mb duplication or deletion on mouse chromosome 7C syntenic with the human 15q13.3 region by gene targeting and trans-allelic recombination in vivo. LoxP sites were inserted into the mouse genome by gene targeting to flank the region to duplicate or delete. Mice were bred that carry the two loxP sites in trans and an Hprt-Cre transgene (RRID:IMSR_JAX:004302). When breeding these mice to wild-type mice, some offspring carried either the duplication or the deletion, demonstrating trans-allelic recombination in the germline, as confirmed by comparative genomic hybridization. Selectable markers were deleted by Flp/FRT-mediated recombination (RRID:IMSR_JAX:003800) prior to combining the loxP alleles in the animal. The mice have been backcrossed to C57BL/6J for at least 10 generations.
Fejgin K, Nielsen J, Birknow MR, Bastlund JF, Nielsen V, Lauridsen JB, Stefansson H, Steinberg S, Sorensen HB, Mortensen TE, Larsen PH, Klewe IV, Rasmussen SV, Stefansson K, Werge TM, Kallunki P, Christensen KV, Didriksen M. A mouse model that recapitulates cardinal features of the 15q13.3 microdeletion syndrome including schizophrenia- and epilepsy-related alterations. Biol Psychiatry. 2014 Jul 15;76(2):128-37. doi: 10.1016/j.biopsych.2013.08.014. Epub 2013 Oct 3. (Medline PMID: 24090792)
Nilsson SRO, Celada P, Fejgin K, Thelin J, Nielsen J, Santana N, Heath CJ, Larsen PH, Nielsen V, Kent BA, Saksida LM, Stensbøl TB, Robbins TW, Bastlund JF, Bussey TJ, Artigas F, Didriksen M. A mouse model of the 15q13.3 microdeletion syndrome shows prefrontal neurophysiological dysfunctions and attentional impairment. Psychopharmacology (Berl). 2016 Jun;233(11):2151-2163. doi: 10.1007/s00213-016-4265-2. Epub 2016 Mar 17. (Medline PMID: 26983414)
Giovanoli S, Werge TM, Mortensen PB, Didriksen M, Meyer U. Interactive effects between hemizygous 15q13.3 microdeletion and peripubertal stress on adult behavioral functions. Neuropsychopharmacology. 2019 Mar;44(4):703-710. doi: 10.1038/s41386-018-0189-3. Epub 2018 Aug 27. (Medline PMID: 30188511)
Gordon A, Forsingdal A, Klewe IV, Nielsen J, Didriksen M, Werge T, Geschwind DH. Transcriptomic networks implicate neuronal energetic abnormalities in three mouse models harboring autism and schizophrenia-associated mutations. Mol Psychiatry. 2021 May;26(5):1520-1534. doi: 10.1038/s41380-019-0576-0. Epub 2019 Nov 8. (Medline PMID: 31705054)
Rees KA, Halawa AA, Consuegra-Garcia D, Golub VM, Clossen BL, Tan AM, Montgomery KS, Samba Reddy D, Griffith WH, Winzer-Serhan UH. Molecular, physiological and behavioral characterization of the heterozygous Df[h15q13]/+ mouse model associated with the human 15q13.3 microdeletion syndrome. Brain Res. 2020 Nov 1;1746:147024. doi: 10.1016/j.brainres.2020.147024. Epub 2020 Jul 23. (Medline PMID: 32712126)
Al-Absi AR, Qvist P, Glerup S, Sanchez C, Nyengaard JR. Df(h15q13)/+ Mouse Model Reveals Loss of Astrocytes and Synaptic-Related Changes of the Excitatory and Inhibitory Circuits in the Medial Prefrontal Cortex. Cereb Cortex. 2021 Feb 5;31(3):1609-1621. doi: 10.1093/cercor/bhaa313. (Medline PMID: 33123721)
Gass N, Weber-Fahr W, Sartorius A, Becker R, Didriksen M, Stensbøl TB, Bastlund JF, Meyer-Lindenberg A, Schwarz AJ. An acetylcholine alpha7 positive allosteric modulator rescues a schizophrenia-associated brain endophenotype in the 15q13.3 microdeletion, encompassing CHRNA7. Eur Neuropsychopharmacol. 2016 Jul;26(7):1150-60. doi: 10.1016/j.euroneuro.2016.03.013. Epub 2016 Mar 28. (Medline PMID: 27061851)
Forsingdal A, Fejgin K, Nielsen V, Werge T, Nielsen J. 15q13.3 homozygous knockout mouse model display epilepsy-, autism- and schizophrenia-related phenotypes. Transl Psychiatry. 2016 Jul 26;6(7):e860. doi: 10.1038/tp.2016.125. (Medline PMID: 27459725)
Kogan JH, Gross AK, Featherstone RE, Shin R, Chen Q, Heusner CL, Adachi M, Lin A, Walton NM, Miyoshi S, Miyake S, Tajinda K, Ito H, Siegel SJ, Matsumoto M. Mouse Model of Chromosome 15q13.3 Microdeletion Syndrome Demonstrates Features Related to Autism Spectrum Disorder. J Neurosci. 2015 Dec 9;35(49):16282-94. doi: 10.1523/JNEUROSCI.3967-14.2015. (Medline PMID: 26658876)
Colony Surveillance Program and Current Health Reports
N10+ (C57BL/6J)
Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.
Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.edu for more information.
A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Sherene Shenouda.
Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.
A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Sherene Shenouda
Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.
1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.
2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.
3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.
4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.
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