129-Hfe^tm1.1Nca/J

Stock number: 005063
Product name: C282Y
Research areas: Hematological Research, Metabolism Research, Mouse/Human Gene Homologs

Description

These Hfe hypomorphic mice exhibit hemochromatosis, accumulating hepatic iron postnatally.

Detailed description

Mice that are homozygous for the targeted mutation are viable and fertile. These mice carry the "C282Y" mutant Hfe allele, which encodes a tyrosine to cysteine amino acid substitution at codon 282. Expression of the missense mutation is detected by RT-PCR analysis. Homozygotes exhibit hemochromatosis, accumulating hepatic iron postnatally. These mice have a phenotype that is intermediate between wildtype mice and mice that are homozygous for the null allele, Hfe^tm2Nca. This mutant mouse strain may be useful in studies of hereditary hemochromatosis.

Development

A targeting vector containing the C282Y missense mutation, a tyrosine to cysteine substitution at codon 282, and neomycin resistance and cytosine deaminase genes was used to insert the missense mutation into the endogenous locus. The construct was electroporated into 129S6/SvEvTac derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts.

Allele

Symbol: Hfe^tm1.1Nca
Name: targeted mutation 1.1, Nancy C Andrews
MGI accession ID: MGI:2385350
Generation method: Targeted
Attributes: Hypomorph; Humanized sequence
Marker symbol: Hfe
Marker name: hemochromatosis
Chromosome: 13
Strain of origin: 129S6/SvEvTac
Molecular note: This hypomorphic allele was generated by targeting exon 4 with a c.881G>A substitution, which causes a cysteine to tyrosine missense mutation at codon 294 (p.C294Y). This mutation is the equivalent of the p.C282Y mutation found in human hereditary hemochromatosis (HE) patients. The substitution disrupts an intramolecular disulfide bond and putatively affects Beta2-microglobulin binding. RT-PCR analysis confirmed the presence of properly spliced transcript in mutant mice. The loxP site flanked neomycin resistance gene cassette that was inserted into intron 4 was removed through cre-mediated recombination.