These mice carry the spontaneous Hertwig’s anemia mutation (an, now identified to be an allele of the Cdk5rap2 gene) and characterized by a mild macrocytic anemia.Read More +
Homozygous mutants are anemic at birth, are small, and usually die within a few days. The anemia can be seen as early 12 days of gestation and persists throughout life. The white cell count is also much reduced. Adult an/an mice of both sexes have fewer definitive germ cells than do normal littermates and seldom produce offspring. Testicular tubules of newborn an/an males contain primordial germ cells, but almost no spermatogenesis is seen in adult testes. Older an/an mice (beyond 6 to 8 months) frequently develop eye opacities, lose their hair completely, and become emaciated and kyphotic
The mutation Hertwig’s anemia (an) was first described in 1941 as an inherited macrocytic anemia that was identified in the offspring of a heavily irradiated male mouse of undefined genetic background. The mutation has since been identified as an allele of the Cdk5rap2 gene and has been highly backcrossed to the C57BL/6J and the WB/Re inbred strains. A semi-dominant light brown pigment marker, tyrosinase-related protein 1; light (TrypB-lt), closely linked to Cdk5rap2an and fixed on both the WB and B6 an stocks during their development, provides a visible phenotypic marker of +/+, an/+, and an/an mice. The exact date and source for importation of this mutation to The Jackson Laboratory is not known, but in 1968 Dr. Elizabeth Russell was maintaining two strains carrying this mutation. The first was a sibling inbred line referred to as BAN/Re because it was maintained with the b allele of Tyrp1 in coupling with the Cdk5rap2an mutation and in 1968 this line was at inbreeding generation F22. The second was a congenic line bearing the Cdk5rap2an mutation in coupling with the semidominant Tyrp1B-lt allele on the C57BL/6J host background and this congenic was at generation N13 in 1968 and N50 in 1978. This strain was passed from Dr. Russell to Dr. Jane Barker and reached generation N73 in 1986. Sperm was cryopreserved in 2007 from Cdk5rap2an Tyrp1B-lt/+ + heterozygous males at generation N96.
|Gene Symbol and Name||Tyrp1, tyrosinase-related protein 1|
|Strain of Origin||C58|
|Molecular Note||A C-to-T transition at coding nucleotide 112 is predicted to result in an arginine to cysteine substitition at codon 38 (p.R38C).|
|Allele Name||Hertwig's anemia|
|Allele Type||Radiation induced (Modified isoform(s))|
|Gene Symbol and Name||Cdk5rap2, CDK5 regulatory subunit associated protein 2|
|Strain of Origin||Not Specified|
|Molecular Note||Exon 4 is inverted which results in an in-frame 111 bp deletion with the loss of exon 4 from the mRNA. Northern analysis demonstrated that exon 4 was uniformly omitted from the mutant mRNA.|
The mutation Hertwig’s anemia is separated from the light brown coat color marker by approximately 2 cM. So long as there is no recombination between these loci the mice homozygous for Hertwig’s anemia will be homozygous for the light mutation and can be identified by their light brown coat color, with brown at the tips of the hair and the rest of the shaft almost white. Male homozygotes are sterile, and on the C57BL/6J background few, if any, homozygotes survive. Heterozygotes have increased brown pigment and can be distinguished from homozygotes as early as 2 weeks of age. Black mice are predicted to be wild-type, lacking even one copy of the Hertwig’s anemia mutation, again contingent upon no recombination between these loci.
When using the Hertwig's anemia mouse strain in a publication, please cite the originating article(s) and include JAX stock #002306 in your Materials and Methods section.