HRS/J

Stock number: 000673
Research areas: Cancer Research, Cardiovascular Research, Dermatology Research, Immunology, Inflammation and Autoimmunity Research, Mouse/Human Gene Homologs, Research Tools

Detailed description

Mice homozygous for the hr spontaneous mutation have a higher incidence and earlier onset of leukemia, reducible by virus-specific antibody. Deficiency of splenic T helper cells (Ly-1+) may account for low cellular immune response of homozygous mutant mice. The coat is normal on hr/hr mice up to 10 days but then hair is lost from the follicle. Waves of hair growth with few thin fuzzy hairs ocur at monthly intervals for some time but homozygotes eventually become continuously hairless. Vibrissae are repeatedly regrown and shed, becoming more abnormal with age. Toenails are long and curved. There is hyperkeratosis of stratified epithelium and the upper part of hair canals beginning at 14 days. Hair club formation is abnormal. Cysts form from the hyperkeratotic upper part of hair canals and sheaths of abnormal follicles stranded in dermis. Some cysts also form from sebaceous glands. All cysts undergo sebaceous transformation and later keratinization. HRS/J mice, fed an atherogenic diet (1.25% cholesterol, 0.5% cholic acid and 15% fat), fail to develop atherosclerotic aortic lesions in contrast to several highly susceptible strains of mice (e.g. C57BL/6J, Stock No. 000664; C57L/J, Stock No. 000668, C57BR/cdJ, Stock No. 000667, and SM/J, Stock No. 000687).

Development

The hairless mutation (Hr^hr) was found in a mouse caught in an aviary in London in 1924. It was brought to The Jackson Laboratory in 1956 by Dr. E. L. Green who had received it from Dr. H. Chase at Brown University in 1952. Dr. Green crossed it to a BALB/c female and the stock was sibling mated. The genotype was fixed homozygous for brown (Tyrp1^b), albino (Tyr^c), dilute (Myo5a^d) and kept segregating for hairless. Since the hairless females do not nurse their litters it was bred hairless males x haired females. In 1964 at generation F24 the strain was named HRS/J. Embryos were cryopreserved in 1992 from haired females mated to hairless males at F90.

Allele

Symbol: Ahr^b-2
Name: b-2 variant
MGI accession ID: MGI:2667355
Generation method: Not Applicable
Marker symbol: Ahr
Marker name: aryl-hydrocarbon receptor
Chromosome: 12
Strain of origin: BALB/cBy
Molecular note: This allele encodes a high affinity, heat labile, 104 kDa receptor containing 848 amino acids. Sequencing studies of cDNA from C57BL/6J congenic mice homozygous for this allele identified nucleotide substitutions in the ORF that would cause 5 amino acid differences between the C57BL/6J and BALB/cBy peptides, and 2 amino acid differences between the BALB/cBy and DBA/2J peptides. A T to C transition in exon 11 replaces the opal termination codon in the C57BL/6J allele with an arginine codon in the BALB/cBy allele. This change would extend translation of the BALB/cBy mRNA by 43 amino acids, accounting for the larger size of the peptide produced by this allele (104 kDa, vs 95 kDa for the C57BL/6J allele).
General note: C57BL/6 carries the responsive Ahr^b allele; DBA/2 carries nonresponsive Ahr^d. Heterozygotes (Ahr^b/Ahr^d) are responsive (J:5282). Later work identified a second (J:8895) and later a third (J:22144) allele conferring response. Thus the allele in C57, C58, and MA/My strains is now Ahr^b-1; Ahr^b-2 is carried by BALB/cBy, A, and C3H; and Ahr^b-3 by Mus spretus, M. caroli, and MOLF/Ei. The nonresponsive strains AKR, DBA/2, and 129 carry Ahrd (J:22144). Nucleotide and amino acid sequence differences between Ahr^b-1 and Ahr^d have been determined (J:17460).

Strain of origin - this allele was found in BALB/cByJ, A/J, C3H/HeJ, CBA strains

Allele

Symbol: Hr^hr
Name: hairless
MGI accession ID: MGI:1856057
Generation method: Spontaneous
Marker symbol: Hr
Marker name: lysine demethylase and nuclear receptor corepressor
Chromosome: 14
Strain of origin: Not Specified
Molecular note: The hr allele is the result of a retroviral integration. Insertion of murine leukemia proviral sequences into intron 6 results in aberrant splicing of the gene.

Allele

Symbol: Myo5a^d
Name: dilute
MGI accession ID: MGI:1856004
Generation method: Spontaneous
Marker symbol: Myo5a
Marker name: myosin VA
Chromosome: 9
Strain of origin: old mutant of the mouse fancy
Molecular note: This mutation is the result of the integration of ecotropic murine leukemia virus Emv-3 into a noncoding region of the Myo5a^d gene. Reversions of Myo5a^d to wild-type are caused by excision of the virus leaving exactly one long terminal repeat in place.

Allele

Symbol: B2m^a
Name: a variant
MGI accession ID: MGI:6357680
Generation method: Spontaneous
Attributes: Not Applicable
Marker symbol: B2m
Marker name: beta-2 microglobulin
Chromosome: 2
Strain of origin: multiple strains
Molecular note: The a variant is slightly slower running on SDS PAGE and was found to have an aspartic acid at amino acid position 85. This allele is found in A, BALB/c, LP and most other strains.