Strain Name:
FVB/NJ-Trpc6em2Jscf/Mmnc
Stock Number:
069742-UNC
Citation ID:
RRID:MMRRC_069742-UNC
Other Names:
Trpc6DN

Strain Information

Trpc6em2Jscf
Name: transient receptor potential cation channel, subfamily C, member 6; endonuclease-mediated mutation 2, Johannes S Schlondorff
Synonyms: Trpc6DN
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 9
Alteration at locus: CRISPR
Trpc6
Name: transient receptor potential cation channel, subfamily C, member 6
Synonyms: Trrp6, mtrp6
Type: Gene
Species: Mouse
Chromosome: 9
Alteration at locus: CRISPR
NCBI: 22068
VEGA: 9
Homologene: 37944
Genetic Alterations
Several base pair changes were introduced into the Trpc6 gene, which together encode for an LFW to AAA pore-mutation (leucine, phenylalanine, and tryptophan to alanines). These mutations have previously been shown to act as a dominant negative in respect to the protein's channel activity. This effect on channel activity was confirmed for this mutation using Fura2 calcium imaging from platelets derived from Trpc6DN/DN and Trpc6+/DN animals.
Genotype Determination
  • Genotyping Protocol(s)
  • Center protocol and contact for technical support will be shipped with mice.
  • ES Cell Line
    Not applicable
    Phenotype
    The Trpc6DN/DN homozygous animals have no overt phenotype. Platelets from these animals do show diminished calcium influx and downstream Erk activation in response to the TRPC3/6/7 agonist, GSK1702934A.In unpublished data, these animals do not develop any proteinuria or histologist renal lesions at baseline and with aging.
    MeSH Terms
    • Animals
    • Blood Platelets/metabolism
    • Calcium/metabolism
    • Gain of Function Mutation
    • Mice
    • Mutation
    • Phosphatidylserines/metabolism
    • Platelet Glycoprotein GPIIb-IIIa Complex/metabolism
    • TRPC Cation Channels/genetics
    • TRPC Cation Channels/metabolism
    • TRPC6 Cation Channel/genetics
    • TRPC6 Cation Channel/metabolism
    Strain Development
    Mice carrying mutant Trpc6 allele were generated at the BIDMC transgenic core using CRISPR/Cas9 with two site-specific guide RNAs (PNA Bio) per locus, Cas9 nickase (PNA Bio), and a single stranded DNA oligo (IDT) carrying the desired mutant sequence. Genomic DNA from founder mice was amplified by PCR and screened by Sanger sequencing. Founders carrying the desired mutation were mated with FVB/NJ mice (Jackson Laboratory). After at least 5 backcrosses with FVB/NJ mice, heterozygous mice were mated to generate homozygous offspring and wild-type littermates. The Trpc6DN/DN line was then maintained by mating homozygous mice.
    Suggested Control Mice
    In published work, Trpc6 WT/DN heterozygous mice were first mated to generate WT/WT and DN/DN littermates. WT/WT mice were mated to each other to generate control animals for offspring of the DN/DN matings. However, FVB/NJ mice from Jackson Labs would be suitable controls in future experiments.
    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.
    • Hematology
    • Internal/Organ
    • Models for Human Disease
    Donor
    Johannes Schlondorff, M.D., Beth Israel Deaconess Medical Center.
    Primary Reference

    Boekell KL, Brown BJ, Talbot BE, Schlondorff JS. Trpc6 gain-of-function disease mutation enhances phosphatidylserine exposure in murine platelets. PLoS One. 2022 Jun 24;17(6):e0270431. doi: 10.1371/journal.pone.0270431. (Medline PMID: 35749414)

    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
    White
    Eye
    Pink
    MMRRC Breeding System
    Sib-mating
    Generation
    n=5
    Overall Breeding Performance
    Excellent
    Viability and Fertility: Female Male Comments
    Homozygotes are viable: Yes Yes
    Homozygotes are fertile: Yes Yes
    Heterozygotes are fertile: Yes Yes
    Age Reproductive Decline: 4 to 6 months 7 to 9 months
    Average litter size
    7 to 9
    Recommended wean age
    3 Weeks
    Average Pups Weaned
    7 to 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@med.unc.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 David McCarthy.

    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 David McCarthy

    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
    069742-UNC-EMBRYO Cryo-preserved embryos $1,404.00 / $2,331.00
    Non-Profit / For-Profit
    Aliquot Approximate quantity2 : 20-40 embryos / aliquot
    069742-UNC-SPERM Cryo-preserved spermatozoa $564.00 / $937.00
    Non-Profit / For-Profit
    Aliquot Approximate quantity3
    069742-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.

    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.