B6;129-Cacna1h^tm1Kcam/J

Stock number: 013770
Product name: α₁3.2-
Strain synonyms: Cav3.2-
Research areas: Cardiovascular Research, Developmental Biology Research

Description

These Cacna1h knock-out mice have constitutively constricted coronary arterioles and focal myocardial fibrosis. This strain may be useful in studies of coronary artery function and disease.

Detailed description

Homozygous Cacna1h (calcium channel, voltage-dependent, T type, alpha 1H subunit; also called α₁ 3.2) targeted mutant mice have constitutively constricted coronary arterioles and focal myocardial fibrosis. Isolated arteries show normal contractile responses but reduced relaxation in response to acetylcholine and nitroprusside. Diffuse areas of cardiac fribrosis are observed in ventricular walls from 10-week old mice, but not those of wildtype mice. At 1 year of age, their hearts have a more severe cardiac pathology, including larger areas of fibrosis, necrosis and lymphocyte infiltration. Homozygotes are smaller than littermate controls. Heterozygotes do not show any abnormalities. Northern and/or Western blot analysis of brain, testis and dorsal root ganglion tissues confirms the loss of RNA and protein in mice. This strain may be useful in studies of coronary artery function and disease.

Development

Exon 6, encoding amino acid residues 216-267, was replaced with a loxP-flanked neomycin resistance cassette in (129X1/SvJ x 129S1/Sv)F1- Kitl⁺-derived R1 embryonic stem (ES) cells. The donating investigator reports that mutant mice were backcrossed to C57BL/6 mice for six generations prior to sending to The Jackson Laboratory Repository (see SNP notes below). Upon arrival, mutant mice were bred to C57BL/6J inbred mice (Stock No. 000664) for one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with markers covering all 19 chromosomes and the X chromosome, was performed on the rederived living colony at The Jackson Laboratory Repository. This revealed markers on Chromosome 4 and 6, and two markers on chromosome 8 that were not fixed for C57BL/6 allele-type (e.g.: still segregating for 129X1/129S1 allele-type markers). These data suggests an incomplete backcross.

Allele

Symbol: Cacna1h^tm1Kcam
Name: targeted mutation 1, Kevin P Campbell
MGI accession ID: MGI:2682015
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cacna1h
Marker name: calcium channel, voltage-dependent, T type, alpha 1H subunit
Chromosome: 17
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: Exon 6, which encodes residues 216 through 267, was replaced with a floxed neo cassette inserted by homologous recombination. Transcript was undetected by Northern blot analysis of RNA obtained from homozygous mutant testes. Similarly, Western blot analysis of extracts from homozygous mutant brain tissue indicated an absence of normal protein.