C3H/HeSnJ

Stock number: 000661
Strain synonyms: C3Sn, C3H Snell, C3H/HeDiSnJ
Research areas: Mouse/Human Gene Homologs, Neurobiology Research, Research Tools, Sensorineural Research

Description

C3H mice are used as a general purpose strain in a wide variety of research areas including cancer, infectious disease, sensorineural, and cardiovascular biology research. This C3H substrain was rederived in the 1960's and again in 1999, as a result, this line does not carry the exogenous mouse mammary tumor virus (MMTV). These mice are homozygous for Clcc1^m1J, which causes increased sensitivity to endoplasmic reticulum stress in the cerebellum, and homozygous for the retinal degeneration allele Pde6b^rd1.

Detailed description

C3H mice are used as a general purpose strain in a wide variety of research areas including cancer, infectious disease, sensorineural, and cardiovascular biology research. The C3H/HeSnJ substrain served as the parental strain for the Snell (Sn) congenic strains. This substrain does not carry the exogenous mouse mammary tumor virus (MMTV) and, like the other C3H strains, is homozygous for the retinal degeneration allele (rd1), but lacks the nob5 allele of Gpr179 (Chang, 2015). Unlike other C3H inbred strains, this strain is homozygous for the Clcc1^m1J allele, which has a more mild phenotype on this background than on the C57BL/6J congenic background (see Stock# 007723). C3H/HeSnJ have pyknotic granule cells in the cerebellum by 2 months of age, and hypoplastic cerebellum with numerous vacuoles by 22 months of age (Jia et al, 2015).

Development

The C3H parent strain was developed by LC Strong in 1920 from a cross of a Bagg albino female with a DBA male followed by selection for high incidence of mammary tumors (LC Strong, 1935). This high incidence resulted from exogenous mouse mammary tumor virus (MMTV) transmitted through the mother's milk. The Jackson Laboratory maintains four C3H substrains, C3H/HeJ (Stock No. 000659), C3H/HeOuJ (Stock No. 000635), C3HeB/FeJ (Stock No. 000658) and C3H/HeSnJ (Stock No. 000661) that are now free of exogenous MMTV. C3H/HeSnJ, C3H/HeJ and C3H/HeOuJ mice previously carried MMTV but were rederived in 1999 during planned efforts to increase the overall health status of the mice and the virus was not reintroduced. A spontaneous mutation occurred in C3H/HeJ sometime between 1960 and 1968 at lipopolysaccharide response locus (mutation in toll-like receptor 4 gene, Tlr4^lps) making C3H/HeJ mice endotoxin resistant while the other three C3H strains are endotoxin sensitive.

Allele

Symbol: Pde6b^rd1
Name: retinal degeneration 1
MGI accession ID: MGI:1856373
Generation method: Spontaneous
Marker symbol: Pde6b
Marker name: phosphodiesterase 6B, cGMP, rod receptor, beta polypeptide
Chromosome: 5
Strain of origin: various
Molecular note: Two mutations have been identified in rd1 mice. A murine leukimia virus (Xmv-28) insertion in reverse orientation in intron 1 is found in all mouse strains with the rd1 phenotype. Further, a nonsense mutation (C-to-A transversion) in codon 347 that results in a truncation eliminating more than half of the predicted encoded protein, including the catalytic domain, has been identified in all rd1 strains of mice. A specific degradation of mutant transcript during or after pre-mRNA splicing is suggested.
General note: The following inbred strains are known to be homozygous for Pde6b: C3H sublines, CBA/J, FVB/NJ, PL/J, SB, SJL/J, and SWR/J.

Allele

Symbol: Clcc1^m1J
Name: mutation 1, Jackson
MGI accession ID: MGI:5618134
Generation method: Spontaneous
Marker symbol: Clcc1
Marker name: chloride channel CLIC-like 1
Chromosome: 3
Strain of origin: C3H/HeSnJ
Molecular note: The mutation is an intracisternal A-particle (IAP) retrotransposon insertion into a C3H/HeSnJ genomic region. The IAP is inserted into intron 2 of the gene and disrupts the normal splicing of the mRNA transcribed from this gene. Resulting in-frame stop codons from the insertion of IAP sequences resulted in severely reduced protein levels in mutant tissues. The retrotransposition of this IAP is a recent event occurring during, or after, the establishment of the C3H/HeSn substrain.