Strain Detail Sheet

Strain Name:
C57BL/6N-Svilem1.1Luna/Mmjax
Stock Number:
071629-JAX
Citation ID:
RRID:MMRRC_071629-JAX
Other Names:
Svil, also known as Svil -/-

Strain Information

Gene Details

Svilem1.1Luna
Name: supervillin; endonuclease-mediated mutation 1, Elizabeth J Luna
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 18
Alteration at locus: Knockout
Svil
Name: supervillin
Synonyms: B430302E16Rik
Type: Gene
Species: Mouse
Chromosome: 18
Alteration at locus: Knockout
NCBI: 225115
Homologene: 25090
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Genetic Alterations
Svil-/- mice have exon 3 deleted in Svil (supervillin) locus resulting in a loss of the long-muscle specific isoform (archvillin, SV2). This strain maybe useful in studies myopathologies including limb-girdle muscular dystrophy.
Genotype Determination
ES Cell Line
iTL BF1 (MGI:7525411)

Strain Description

Phenotype
Svil (supervillin) encodes a bipartite protein that functions as a membrane-cytoskeleton linker protein that is a scaffold for ERK1/2 signaling. The long-muscle specific isoform (archvillin, SV2) interacts with Sgcg (sarcoglycan, gamma [dystrophin-associated glycoprotein]) a component of the sarcoglycan complex that links the striated muscle cytoskeleton to the basal lamina. Defects in sarcoglycan complex are associated with limb-girdle muscular dystrophy.

Svil-/- mice have exon 3 deleted using CRISPR/cas9 genome editing. Deletion of exon 3 eliminates the long-muscle specific isoform (archvillin, SV2), but allows expression of the nonmuscle isoform supervillin (SV1). SV1 regulates focal adhesion formation and cell survival. Females homozygous for the deletion are viable, but subfertile and exhibit a skewed gender ratio at weaning (2:1, male:female), and gender-specific differences in muscle myofiber composition and glucose uptake.

Mice heterozygous for the mutation are viable and fertile. Females homozygous for the deletion are viable, but subfertile, are poor mothers, and exhibit a skewed gender ratio at weaning (2:1, male:female).
Strain Development
CRISPR/cas9 endonuclease-mediated genome editing was used to replace a 609 nucleotide region in exon 3 of the Svil locus on chromosome 18 with a loxP site upstream of exon 3 and a loxP and FRT-flanked ivNeo selection cassette flanked by 759 bp and 838 bp of genomic sequence downstream of exon 3. gRNAs (5'-TGT AGG GCG ATC CAA AGA AGAAG-3' and 5'-TCT TCA ATG CTT ACC TGG CTCGG-3') and cas9 endonuclease were electroporated into C57BL/6-derived iTL BF1 ES cells carrying a flp recombinase (inGenious). The neo cassette was removed by flp-mediated recombination in the ES cells. Svil transcript Svil-201 (ENSMUST00000024236) was used as reference for the exon number and guide sequences. Some transcripts initiated at internal IRESs encoding C-terminal supervillin/archvillin protein sequences are still expressed. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6NCrl mice for germline transmission. The deletion was confirmed by sequencing and PCR. Mice were backcrossed to C57BL/6NCrl for at least 4 generations. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes.
Suggested Control Mice

C57BL/6NJ

MMRRC Genetic QC

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 csmmrrc@jax.org. Older strains may not have this information.

Research Applications

  • Cancer
  • Cardiovascular
  • Cell Biology
  • Diabetes
  • Models for Human Disease
  • Obesity
  • Reproduction

Strain Origin

Donor
Elizabeth Luna, University of Massachusetts Medical School.
Primary Reference
In preparation, submitted, or in press

Colony and Husbandry Information

Special Considerations

Breeding is most successful with 3-mo males and 10- to 12-week-old females. Expect two surviving litters from 5 breeder females. Pups, especially female pups, are often lost before weaning; the gender ratio is about 2:1 male to female at weaning. We feed the breeders with PicoLab Hi-Fat Mouse Diet 20, Lab Diet #5058. When the females are obviously pregnant, we supplement with sterilized Bio-Serv Chocolate Mini-Treats, S05472-1. Males are usually large enough to wean at 3 weeks. If the dam is not pregnant with a second litter, we leave the females in their birth cage until 4 weeks of age. Second litters are few and generally small.

Health Status Report

For more information about this colony's health status contact csmmrrc@jax.org

Appearance

Coat Color
Black
Eye
Black

Breeding

MMRRC Breeding System
Random intra-strain mating
Generation
N=4.
Overall Breeding Performance
Good

Reproductive Statistics

Viability and Fertility: Female Male Comments
Homozygotes are viable: Reduced Yes
Homozygotes are fertile: Reduced Yes
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: 4 to 6 months Less than 4 months
Average litter size
7 to 9
Recommended wean age
4 Weeks
Average Pups Weaned
4 to 6

Order Request Information

Availability Level

Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at csmmrrc@jax.org for more details.

Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

Conditions of Distribution

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.

Fees

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
071629-JAX-HET-F
071629-JAX-HET-M
071629-JAX-WT-F
071629-JAX-WT-M
Heterozygous / Hemizygous Female
Heterozygous / Hemizygous Male
Wild Type Female
Wild Type Male
 $218.00 / $218.00
Non-Profit / For-Profit		 Per Mouse The csmmrrc@jax.org may assess additional fees for any special requests (e.g., specific age or weight of mice, etc.).
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

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.