STOCK Cacna1c^tm3Hfm/J

Stock number: 024714
Product name: Ca_v1.2 loxP
Research areas: Neurobiology Research, Research Tools

Description

Exons 14 and 15 of the mouse Cacna1c gene are flanked by loxP sites in this conditional knockout strain. L-type calcium channel dysregulation has been implicated in pathologies of the heart as well as skeletal muscle myopathies and neurodegenerative diseases.

Detailed description

The L-type calcium channels are central regulators of intracellular calcium influx and excitation-contraction coupling in striated muscle, as well as excitability and calcium-mediated signaling in neurons. L-type calcium channel dysregulation has been implicated in pathologies of the heart, such as QT prolongation, as well as skeletal muscle myopathies and neurodegenerative diseases. Cacna1c (calcium channel, voltage-dependent, L type, alpha 1C subunit; also called Ca_v1.2), encodes the alpha subunit and pore-forming component of the L-type voltage-dependent calcium channel.

Exons 14 and 15 of the mouse Cacna1c gene are flanked by loxP sites in this conditional mutant strain. In the absence of Cre recombinase mice are viable and show no overt phenotype. Cre-mediated recombination produces a frameshift resulting in a premature stop codon and loss of protein. Homozygous knockout embryos die before embryonic day 14.5, but demonstrate a normal heartbeat at embryonic day 12.5.

Development

A neomycin resistance cassette and herpes simplex virus type I-thymidine kinase cassette (HSV-TK) flanked by loxP sites was inserted into intron 13 of the Cacna1c (calcium channel, voltage-dependent, L type, alpha 1C subunit) gene. A third loxP site was placed in intron 15. The mutation was introduced to (129X1/SvJ x 129S1/Sv)F1- Kitl⁺-derived R1 embryonic stem (ES) cells by homologous recombination. Resultant chimeric males were crossed with C57BL/6 females. The neomycin cassette has been excised with cre recombinase, leaving exons 14 and 15 flanked by loxP sites. This strain was maintained on a mixed 129, C57BL/6 and FVB genetic background by the donating laboratory.

Allele

Symbol: Cacna1c^tm3Hfm
Name: targeted mutation 3, Franz Hofmann
MGI accession ID: MGI:2674119
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Cacna1c
Marker name: calcium channel, voltage-dependent, L type, alpha 1C subunit
Chromosome: 6
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: Exons 14 and 15 were left flanked by single loxP sites. This allele was generated using ES cells that were also used to generate Cacna1c^tm2Hfm.