Strain Name:
B6(129S4)-Myo7atm1c(EUCOMM)Wtsi/SboyeMmmh
Stock Number:
067354-MU
Citation ID:
RRID:MMRRC_067354-MU
Other Names:

Myo7a Conditional Ready (tm1c)

Strain Information

Myo7atm1c(EUCOMM)Wtsi
Name: myosin VIIA; targeted mutation 1c, Wellcome Trust Sanger Institute
Synonyms: Myo7afl
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 7
Alteration at locus: Conditional
Myo7a
Name: myosin VIIA
Synonyms: Myo7, USH1B, nmf371, polka, Hdb
Type: Gene
Species: Mouse
Chromosome: 7
Alteration at locus: Conditional
NCBI: 17921
HGNC: HGNC:7606
Homologene: 219
Genetic Alterations

These mice are conditional-ready tm1c mice, Flp-modified from the original Myo7atm1a(EUCOMM)Wtsi allele. They have also been backcrossed onto a C57BL/6J background and are now free of the Crb1rd8 retinal degeneration allele (MGI:2676366) inherent to the original C57BL/6N background.

The L1L2_Bact_P cassette was inserted at position 98095169 of Chromosome 7 upstream of the critical exon 10 (Build GRCm38). This initial cassette was composed of an FRT site followed by a lacZ sequence and a loxP site. The first loxP site was followed by a neomycin resistance gene under the control of the human beta-actin promoter, SV40 polyA, a second FRT site, and a second loxP site. A third loxP site was inserted downstream of exon 11 at position 98093985. Critical exons 10 and 11 were thus flanked by loxP sites.

ES Cell Line
JM8A3.N1 derived from C57BL/6N
Phenotype

These mice do not display any abnormal phenotypes. Prior to archival at the MMRRC, they were maintained through homozygous x homozygous breeding. There were no issues with the viability/fertility. Importantly, this line has been confirmed to be free of the C57BL/6N-associated Crb1rd8 allele, which, in the homozygous state, leads to retinal degeneration. All mice in KOMP were made on the C57BL/6N background. This has confounded many studies of gene function in the retina.

The Myo7a Conditional-Ready mouse line, when crossed with appropriate Cre driver lines, would be useful in separating and studying the individual effects of Myo7a knockout in the cochlea and vestibular system as reported in PMID:31824252. Systemic knockout of Myo7a through the deletion of critical exons 10 and 11 results in null-expression of MYO7A, which, in humans, is associated with Usher’s Syndrome type 1B (USH1B). This is a multi-organ disease in which affected human patients are born profoundly deaf with vestibular dysfunction. In addition, USH1B patients begin to progressively lose their vision within the first decade of life. Due to the multiple systems affected in USH1B, the Myo7a Conditional-Ready mice provide a valuable tool for researchers. Myo7a Conditional-Ready mice, when crossed with appropriate Cre driver lines, will allow researchers to isolate and investigate the role of MYO7A in individual sensory systems (i.e. auditory vs. vestibular vs. visual systems).
Tm1d Myo7a knockout mice display these same characteristics as previous Myo7a knockout models, namely deafness and vestibular dysfunction (i.e., "shaker" phenotype). However, a novel finding was that, while Myo7a knockout mice are profoundly deaf with highly disorganized/degenerated cochlear hair cells, the vestibular hair cells of these mice are still present.
MeSH Terms
  • Alleles
  • Animals
  • Computational Biology
  • Embryonic Stem Cells/cytology
  • Embryonic Stem Cells/metabolism
  • Gene Deletion
  • Gene Knockout Techniques/methods
  • Genes/genetics
  • Genes, Lethal/genetics
  • Genetic Association Studies/methods
  • Genetic Vectors/genetics
  • Genome/genetics
  • Genomics
  • Genotype
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout/genetics
  • Mutagenesis, Insertional/methods
  • Phenotype
  • Polymerase Chain Reaction
  • Rats
  • Breeding
  • Germ Cells/cytology
  • Mice, Mutant Strains/genetics
  • Quality Control
Strain Development

These mice were generated as part of the Sanger Mouse Genetics Project (PMID:23912999). Mouse ES cells were created as part of the International Knockout Mouse Consortium and were acquired from the Sanger Institute. The knockout-first allele (tm1a) was generated using JM8A3.N1 (C57BL/6N) ES cells. ES cells were implanted in C57BL/6N mice. Resulting tm1a mice were backcrossed on the C57BL/6J background and screened to ensure the removal of the Crb1rd8 allele. Resultant weans were crossed with B6.129S4-Gt(ROSA)26Sortm1(FLP1)Dym/RainJ (RRID:IMSR_JAX:009086) to create the Myo7a conditional-ready (tm1c) strain. These mice have been backcrossed minimally twice to C57BL/6J and sib-mated to F13.

Suggested Control Mice
C57BL/6J
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
  • Research Tools
  • Sensorineural
Donor
Shannon Boye, Ph.D., University of Florida, School of Medicine.
Primary Reference

Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A. A conditional knockout resource for the genome-wide study of mouse gene function. Nature. 2011 Jun 15;474(7351):337-42. doi: 10.1038/nature10163. (Medline PMID: 21677750)

Ryder E, Gleeson D, Sethi D, Vyas S, Miklejewska E, Dalvi P, Habib B, Cook R, Hardy M, Jhaveri K, Bottomley J, Wardle-Jones H, Bussell JN, Houghton R, Salisbury J, Skarnes WC; Sanger Mouse Genetics Project, Ramirez-Solis R. Molecular characterization of mutant mouse strains generated from the EUCOMM/KOMP-CSD ES cell resource. Mamm Genome. 2013 Aug;24(7-8):286-94. doi: 10.1007/s00335-013-9467-x. Epub 2013 Aug 4. (Medline PMID: 23912999)

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 and sib-mating

Generation

N2+ (C57BL/6J), F13

Overall Breeding Performance
Good
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: 7-9 months 10-12 months
Bred to Homozygosity
Yes
Average litter size
7-9
Recommended wean age
3 weeks
Average Pups Weaned
7-9

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.

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.

The donor or their institution limits the distribution to non-profit institutions only.

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
067354-MU-SPERM Cryo-preserved spermatozoa $437.00 / Non-Profit Aliquot Approximate quantity3
067354-MU-RESUS Litter recovered from cryo-archive $2,624.00 / Non-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.

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.