Loading...

Strain Detail Sheet

Strain Name:
B6.Cg-Crb1rd8Arhgef12Tvrm266/PjnMmjax
Stock Number:
071684-JAX
Citation ID:
RRID:MMRRC_071684-JAX
Other Names:
JR30497 B6.Cg-Crb1rd8 Arhgef12Tvrm266/Pjn

Strain Information

Gene Details

Crb1rd8
Name: crumbs family member 1, photoreceptor morphogenesis associated; retinal degeneration 8
Synonyms: Crb16N, nmf144, Rd8-
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 1
Alteration at locus: Chemically Induced
Arhgef12Tvrm266
Name: Rho guanine nucleotide exchange factor 12; translational vision research model 266
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 9
Alteration at locus: Chemically Induced
Arhgef12
Name: Rho guanine nucleotide exchange factor 12
Synonyms: LARG, 2310014B11Rik
Type: Gene
Species: Mouse
Chromosome: 9
Alteration at locus: Chemically Induced
NCBI: 69632
VEGA: 9
Homologene: 9088

Additional Resources
IMPC
Google
Entrez
PubMed
IMSR
Gene Ontology
BioGPS
Gene Cloud
IGTC
Mouse Phenome DB
Mouse Mine
KOMP Phenotyping
Monarch
GeneCards
ClinGen
Genetic Alterations
Tvrm266 mice carry a recessive spontaneous mutation of the Crb1 gene (rd8), characterized by retinal dysplasia, as well as an ENU-induced point mutation in the Arhgef12 gene (c.71T>A). These mice may be useful for studying retinal dysplasia.

Genotype Determination
ES Cell Line
Not applicable

Strain Description

Phenotype
Crumbs family member 1, photoreceptor morphogenesis associated protein (CRB1) is essential for the development of retinal photoreceptors. Mutations in the Crb1 gene have been associated with retinal dysplasia and retinopathies. Rho GTPases play a key role in numerous cellular pathways including spatio-temporal coordination of cytoskeletal dynamics during cell migration. Mutations in the rho guanine nucleotide exchange factor 12 (Arhgef12) gene have been associated with acute myeloid leukemia.

These Tvrm266 mice harbor a spontaneous mutation in the Crb1 gene (rd8), resulting in retinal dysplasia, and an ENU-induced point mutation in Arhgef12 gene (c.71T>A) leading to an early stop signal at codon 24.

The donating laboratory has indicated that homozygous C57BL/6J congenic Crb1rd8 mice have a mild retinal dysplasia phenotype; however, when the Arhgef12 c.71T>A mutation is present with the Crbr1rd8 mutation, the associated eye phenotype is much more severe. This suggests that Arhgef12 may be a modifier gene that differentially shapes CRB1-associated retinal disease. Mice that are homozygous for both Crb1rd8 and Arhgef12Tvrm266 are viable and fertile. These mice may be useful for studying retinal dysplasia.
MeSH Terms
  • Animals
  • Disease Models, Animal
  • Eye Proteins/genetics
  • Eye Proteins/metabolism
  • Isoenzymes/genetics
  • Isoenzymes/metabolism
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism
  • Protein Kinase C/genetics
  • Protein Kinase C/metabolism
  • Retina/metabolism
  • Retinal Degeneration/genetics
  • Retinal Degeneration/metabolism
  • Retinal Degeneration/pathology
  • Retinal Dysplasia/genetics
  • Retinal Dysplasia/metabolism
  • Retinal Dysplasia/pathology
  • Rho Guanine Nucleotide Exchange Factors/genetics
  • Rho Guanine Nucleotide Exchange Factors/metabolism
Strain Development
The Tvrm266 mouse model was generated through ENU mutagenesis of B6.Cg-Crb1rd8 mice. In a fundus phenotypic screen, one strain was identified that displayed an increased spotting fundus phenotype associated with retinal dysplasia. A nonsense mutation (c.71T>A) was identified by whole-exome sequencing in the rho guanine nucleotide exchange factor (12Arhgef12) locus on chromosome 9. This strain was backcrossed to B6.Cg-Crb1rd8 mice for at least four generations by the donating laboratory in an effort to remove any extraneous ENU-generated mutations not linked to the phenotype. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

B6.Cg-Crb1rd8 generation: the mutation in the rd8 mouse has been identified as a single base deletion of a C (G on forward strand) at coding nucleotide 3481 in the gene. This deletion causes a frame shift and a premature stop codon that truncates the transmembrane and cytoplasmic domain of the protein after amino acid 1207. This mutation has been found to be present in all sublines of C57BL/6N and in C57BL/6ByJ, but not in any C57BL/6J subline. This mutation was backcrossed to C57BL/6J for 7 generations by the Nishina laboratory (The Jackson Laboratory). The resulting B6.Cg-Crb1rd8 mice were used for ENU mutagenesis as described above.

Suggested Control Mice
C57BL/6J or C57BL/6J-rd8

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

  • Sensorineural

Strain Origin

Donor
Patsy Nishina, Ph.D., Jackson Laboratories.
Primary Reference

Weatherly SM, Collin GB, Charette JR, Stone L, Damkham N, Hyde LF, Peterson JG, Hicks W, Carter GW, Naggert JK, Krebs MP, Nishina PM. Identification of Arhgef12 and Prkci as genetic modifiers of retinal dysplasia in the Crb1rd8 mouse model. PLoS Genet. 2022 Jun 8;18(6):e1009798. doi: 10.1371/journal.pgen.1009798. (Medline PMID: 35675330)

Colony and Husbandry Information

Special Considerations

N/A

Health Status Report

Cryo-recovered strains distributed by the MMRRC at JAX are shipped to the customer from the Pathogen & Opportunistic-Free Animal Room G200 - see https://www.jax.org/jax-mice-and-services/customer-support/customer-service/animal-health/health-status-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 csmmrrc@jax.org.

Appearance

Coat Color
Black
Eye
Black

Breeding

MMRRC Breeding System
Sib-mating
Generation
NE4
Overall Breeding Performance
Good

Reproductive Statistics

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

Order Request Information

Availability Level

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 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
071684-JAX-SPERM Cryo-preserved spermatozoa $459.00 / $459.00
Non-Profit / For-Profit		 Aliquot Approximate quantity3
071684-JAX-RESUS Litter recovered from cryo-archive $2,123.00 / $2,123.00
Non-Profit / For-Profit		 Litter Recovered litter4; additional fees for any special requests.
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.