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This mouse line carries a premature stop codon in the Cacna1c gene (Gene ID12288), which results in the expression of Cav1.2 channels C-terminally truncated (cutting 343 AAs; WT: 2139 AA, mutant: 1796 AA) at Gly-1796 with an extension of Leu-Ser-Lys-STOP, as well as an alternatively spliced, second variant ending at Gly-1796 with a LSATPERAREPR extension. It is a targeted mutation that PMID2126955 call "KO" in the figures; this should not be confused with ablation of part of or the entire gene.
Homozygous: Homozygous mice die prematurely (E15-P1).
Hetero/Hemizygous: Heterozygous mice containing one truncated allele show no distinguishable phenotypic differences from WT littermates.
Cre-excised Phenotype: Undetermined
A mouse line carrying a premature stop codon that results in the expression of the truncated channel was generated. Approximately 11.5 kb of the Cacna1c gene containing exons 44 through 49 were isolated from a 129SvJ mouse genomic library. A targeting vector was constructed containing 1.1 kb of intronic sequence that extended from a site 0.3 kb upstream of exon 44 as its short arm followed by a 1.9-kb neomycin positive-selection cassette flanked by loxP sites and a 11.2-kb long arm that began at a site 0.3 kb upstream of exon 44 and extended to the NsiI site downstream of exon 49. To truncate the C terminus of CaV1.2 channels after G1796, a three-way stop codon cassette (5_-ctgagtaagta) was ligated into the NcoI site in exon 44 of the targeting construct. An NcoI-linearized targeting construct was transfected into 129Sv/Ev embryonic stem cells by electroporation. Clones were selected and expanded in the presence of G418. PCR analysis was used to identify clones that had undergone homologous recombination. The correctly targeted embryonic stem cell clones were microinjected into C57BL/6J blastocysts (The Jackson Laboratory, Bar Harbor, ME). Germ line transmission of the mutated Cacna1c allele was confirmed for one of three chimeric mice, and the resulting progeny were backcrossed into C57Bl/6J for more than 10 generations to generate heterozygous (Het) and homozygous CaV1.2_DCT (KO) animals.
Fu, Y., Westenbroek, R.E., Yu, F.H., Clark, J.P. 3rd, Marshall, M.R., Scheuer, T., Catterall, W.A. Deletion of the distal C-terminus of Cav1.2 channel leads to loss of Beta-adrenergic regulation and heart failure in vivo. J Biol Chem. 2011 Apr 8;286(14):12617-26. Epub 2011 Jan 7. (Medline PMID: 21216955)
Marshall, M.R., Clark, J.P., Westenbroek, R., Yu, F.H., Scheuer, T., Catterall, W.A. Functional roles of a C-terminal signaling complex of Cav1 channels and A kinase anchoring protein-15 in brain neurons. J Biol Chem. 2011 Apr 8;286(14):12627-39. Epub 2011 Jan 11. (Medline PMID: 21224388)
Colony Surveillance Program and Current Health Reports
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.
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.