B6.Cg-Cdk5rap2^an Tyrp1^B-lt/+ +/BrkJ

Stock number: 002306
Product name: Hertwig's anemia
Research areas: Cancer Research, Hematological Research, Reproductive Biology Research, Research Tools

Description

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.

Detailed description

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

Development

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 (Tryp^B-lt), closely linked to Cdk5rap2^an 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 Cdk5rap2^an mutation and in 1968 this line was at inbreeding generation F22. The second was a congenic line bearing the Cdk5rap2^an mutation in coupling with the semidominant Tyrp1^B-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 Cdk5rap2^an Tyrp1^B-lt/+ + heterozygous males at generation N96.

Allele

Symbol: Cdk5rap2^an
Name: Hertwig's anemia
MGI accession ID: MGI:1856646
Generation method: Radiation induced
Attributes: Modified isoform(s)
Marker symbol: Cdk5rap2
Marker name: CDK5 regulatory subunit associated protein 2
Marker synonyms: 2900018K03Rik; an; C48; Cep215; MCPH3; MGC:38528; mKIAA1633
Chromosome: 4
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.

Allele

Symbol: Tyrp1^B-lt
Name: light
MGI accession ID: MGI:1855962
Generation method: Spontaneous
Marker symbol: Tyrp1
Marker name: tyrosinase-related protein 1
Marker synonyms: b-PROTEIN; CAS2; CATB; GP75; isa; OCA3; TRP; TRP1; TRP-1; TYRP
Chromosome: 4
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).