Strain Name:
129S6(Cg)-Ryr2tm1.1Msnr/Mmnc
Stock Number:
036932-UNC
Citation ID:
RRID:MMRRC_036932-UNC
Other Names:
Ryr2ADA/ADA

Strain Information

Ryr2tm1.1Msnr
Name: ryanodine receptor 2, cardiac; targeted mutation 1.1, Gerhard Meissner
Synonyms: Ryr2tm1Msnr, Ryr2ADA
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 13
Alteration at locus: Knock-In
Ryr2
Name: ryanodine receptor 2, cardiac
Synonyms: 9330127I20Rik
Type: Gene
Species: Mouse
Chromosome: 13
Alteration at locus: Knock-In
NCBI: 20191
VEGA: 13
Homologene: 37423
Genetic Alterations
Three amino acid (W3587A/L3591D/F3603A; ADA) mutations were inserted to exon 75 of RyR2 gene, which eliminates calmodulin-dependent inhibition of Ryr2 activity. A floxed neo was subsequently removed via cre-mediated recombination.
Genotype Determination
  • Genotyping Protocol(s)
  • Center protocol and contact for technical support will be shipped with mice.
  • ES Cell Line
    TC1/TC-1 derived from 129S6/SvEvTac
    Phenotype

    Homozygous: Ryr2ADA/ADA mice show signs of cardiac hypertrophy at day 1 after birth and die ~2 weeks after birth.

    Heterozygous: Ryr2+/ADA mice live longer than 1 year and show only minor signs of cardiac hypertrophy.

    Mammalian Phenotype Terms
    Allelic Composition: Ryr2tm1.1Msnr/Ryr2tm1.1Msnr (Genetic Background: involves: 129S6/SvEvTac * FVB/N )

    Allelic Composition: Ryr2tm1.1Msnr/Ryr2+ (Genetic Background: involves: 129S6/SvEvTac * FVB/N )

    MeSH Terms
    • Amino Acid Substitution/genetics
    • Animals
    • Calmodulin/physiology
    • Cardiomegaly/genetics
    • Cardiomegaly/metabolism
    • Cardiomegaly/pathology
    • Mice
    • Mutagenesis, Site-Directed
    • Myocardium/metabolism
    • Ryanodine Receptor Calcium Release Channel/genetics
    • Ryanodine Receptor Calcium Release Channel/metabolism
    • Calcineurin/genetics
    • Calcineurin/physiology
    • Cardiomegaly/physiopathology
    • Extracellular Signal-Regulated MAP Kinases/physiology
    • Female
    • Glycogen Synthase Kinase 3/physiology
    • Glycogen Synthase Kinase 3 beta
    • Heart/embryology
    • Heart/physiopathology
    • Male
    • Mice, Knockout
    • Mice, Transgenic
    • Models, Animal
    • NFATC Transcription Factors/physiology
    • Proto-Oncogene Proteins c-akt/physiology
    • Ribosomal Protein S6 Kinases, 90-kDa/physiology
    • Ryanodine Receptor Calcium Release Channel/physiology
    • Signal Transduction/physiology
    • DNA/genetics
    • DNA Nucleotidyltransferases/genetics
    • Eye Neoplasms/genetics
    • Genome
    • Integrases
    • Lens, Crystalline/pathology
    • Transgenes
    • Viral Proteins
    • Zygote
    Strain Development
    Linearized targeting vector was electroporated into TC1 ES cells derived from 129S6/SvEvTac. Correctly targeted ES cells were injected into the blastocysts of C57BL/6J mice. A male chimera mouse carrying mutations in Ryr2 gene was mated with a 129S6/SvEvTac female mouse to obtain heterozygous offspring. The neomycin resistant gene flanked by loxP sequences was removed by breeding to a mouse carrying transgene of Cre recombinase driven by EIIa promoter.
    Suggested Control Mice
    Wild-type littermates
    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@med.unc.edu. Older strains may not have this information.
    • Cardiovascular
    • Research Tools
    Donor
    Gerhard Meissner, Ph.D., University of North Carolina.
    Primary Reference

    Yamaguchi N, Takahashi N, Xu L, Smithies O, Meissner G. Early cardiac hypertrophy in mice with impaired calmodulin regulation of cardiac muscle Ca release channel. J Clin Invest. 2007 May;117(5):1344-53. Epub 2007 Apr 12. (Medline PMID:17431507)

    Yamaguchi N, Chakraborty A, Pasek DA, Molkentin JD, Meissner G. Dysfunctional ryanodine receptor and cardiac hypertrophy: role of signaling molecules. Am J Physiol Heart Circ Physiol. 2011 Jun;300(6):H2187-95. Epub 2011 Mar 18. (Medline PMID: 21421818)

    Lakso M, Pichel JG, Gorman JR, Sauer B, Okamoto Y, Lee E, Alt FW, Westphal H. Efficient in vivo manipulation of mouse genomic sequences at the zygote stage. Proc Natl Acad Sci U S A. 1996, Jun 11;93(12):5860-5. (Medline PMID: 8650183)

    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_health@med.unc.edu.
    Coat Color
    Grey/brown
    MMRRC Breeding System
    Backcross
    Breeding Scheme(s)

    Wild-type (129S6/SvEvTac) female x Heterozygous male or reciprocal mating

    Generation
    N15+
    Overall Breeding Performance
    Excellent
    Viability and Fertility: Female Male Comments
    Homozygotes are viable: Reduced Reduced Offsprings die about 2 weeks after birth.
    Homozygotes are fertile: N/A N/A
    Heterozygotes are fertile: Yes Yes
    Age Reproductive Decline: 8 months 12 months
    Average litter size
    5-9
    Recommended wean age
    3 weeks

    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@med.unc.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.

    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
    036932-UNC-RESUS Litter recovered from cryo-archive $2,914.00 / $4,837.00
    Non-Profit / For-Profit
    Litter Recovered litter4; additional fees for any special requests.
    Cryopreserved material may be available upon request, please inquire to mmrrc@med.unc.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.