Strain Name:
B6.Cg(129S1)-Del(7Chrna7-Fan1)1Uru/UruMmmh
Stock Number:
068235-MU
Citation ID:
RRID:MMRRC_068235-MU
Other Names:
15q13.3 deletion mice; B6.Cg(129S1)-Del(7Chrna7-Fan1)1Uru

Strain Information

Del(7Chrna7-Fan1)1Uru
Name: deletion, Chr 7, Uwe Rudolph 1
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 7
Chrna7
Name: cholinergic receptor, nicotinic, alpha polypeptide 7
Synonyms: Acra7, alpha7, alpha7 nicotinic receptor, alpha7-nAChR
Type: Gene
Species: Mus musculus (mouse)
Chromosome: 7
NCBI: 11441
Homologene: 593
Fan1
Name: FANCD2/FANCI-associated nuclease 1
Synonyms: 6030441H18Rik, Mtmr15
Type: Gene
Species: Mus musculus (mouse)
Chromosome: 7
NCBI: 330554
Homologene: 45598
Genetic Alterations
Combination of two gene targetings to generate two loxP sites followed by trans-allelic recombination in vivo to generate the genomic 1.4-Mb deletion.

For the 15q13.3 deletion (MMRRC:68235) and duplication (MMRRC:68236), the deleted or duplicated genes are:

  • Fan1 (Fanconi-associated nuclease 1),
  • Mtmr10 (myotubularin related protein 10),
  • Trpm1 (transient receptor potential cation channel, subfamily M, member 1),
  • Klf13 (Kruppel-like factor 13),
  • Otud7a (ovarian tumor domain deubiquitinase 7A, and
  • Chrna7 (nicotinic acetylcholine receptor a7 subunit).
ES Cell Line
v6.5 derived from (C57BL/6 x 129S4/SvJae)F1
Phenotype

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).

Strain Development

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.

Suggested Control Mice
Wild-type offspring of a cross of hemizygous mice and C57BL/6J wild-type mice
MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@missouri.edu. Older strains may not have this information.
  • Models for Human Disease
  • Neurobiology
Donor
Uwe Rudolph, M.D., University of Illinois at Urbana-Champaign.
Primary Reference
Not ready to publish
Additional References

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 and Husbandry Information

Colony Surveillance Program and Current Health Reports

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@missouri.edu .
Coat Color
Black
Eye
Black
MMRRC Breeding System
Backcross
Generation

N10+ (C57BL/6J)

Overall Breeding Performance
Excellent
Viability and Fertility: Female Male Comments
Homozygotes are viable: Undetermined Undetermined
Homozygotes are fertile: Undetermined Undetermined
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: 10 to 12 months 10 to 12 months
Bred to Homozygosity
Yes
Average litter size
4 to 6
Recommended wean age
3 Weeks
Average Pups Weaned
4 to 6

Order Request Information

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.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
068235-MU-SPERM Cryo-preserved spermatozoa $437.00 / $817.00
Non-Profit / For-Profit
Aliquot Approximate quantity3
068235-MU-RESUS Litter recovered from cryo-archive $2,624.00 / $5,340.00
Non-Profit / For-Profit
Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.edu for more information.

Some MMRRC strains were submitted by the donor as cryopreserved germplasm, and because these strains were not cryopreserved by the MMRRC, we have not assessed the quality of this material. We have extensive experience with recovery of mice from cryopreserved sperm and embryos of varying quality, including using techniques such as IVF and ICSI, and are confident that we will have success in most, if not all, cases. However, because of the unknown quality of these frozen samples, we will restrict recovery efforts to two attempts for each order. Subsequent attempts can be performed on a fee-for-service basis, in addition to the standard fees, upon request.

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.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.