STOCK Oca2^p-d/Oca2^p-25H/J

Stock number: 001585
Research areas: Dermatology Research, Endocrine Deficiency Research, Mouse/Human Gene Homologs, Reproductive Biology Research

Description

These mice are heterozygous for two different alleles of oculocutaneous albinism II (Oca2): Oca2^p-d (dark pink-eye) and Oca2^p-25H (pink-eyed dilution 25 Harwell). The compound heterozygotes have a color phenotype intermediate between those of the two homozygotes with eyes lighter at birth than those of Oca2^p-d mice, but not as light as those of Oca2^p mice, and darken by weaning.

Detailed description

Oca2^p-25H/Oca2^p-25H mice exhibit significant dilution of coat color with pink eyes, similar in appearance to Oca2^p/Oca2^p mice. The Oca2^p-25H phenotype also includes a slightly jerky gait with some tremor, small body size compared to control littermates, male sterility, female semisterility, and impaired maternal behavior, and the smaller-than-expected proportion of Oca2^p-25H homozygous intercross offspring implies reduced prenatal viability (Lyon et al. 1992, Phillips et al. 1977). The Oca2^p-25H mutation comprises an inversion of a segment of Chromsome 7 that alters the 5' end of the Oca2^p gene so that no detectable ptranscript is produced, accounting for the pigment-dilution phenotype (Gardner et al. 1992). The deletion also disrupts the Herc2/rjs gene proximal to Oca2^p so the transcript sequence diverges from wild-type after the first 8772 bp (of 15 kb in wild-type), resulting in a truncated protein and accounting for the non-pigment related aspects of the Oca2^p-25H phenotype (Lehman et al. 1998). Mice homozygous for Oca2^p-d are born with lightly pigmented eyes, darker than those of Oca2^p/Oca2^p mice, which darken by weaning and a coat color "considerably darkerthan that of Oca2^p/Oca2^p mice, somewhat resembling that of brown [Tyrp1^b/Tyrp1^b] mice"; both sexes are fertile (Gardner et al. 1977, Lyon et al. 1992). A normal-sized Oca2^p transcript is present in eyes of Oca2^p-d/Oca2^p-d mice (Gardner et al. 1992), and Southern blot analysis revealed no gross alteration of the Oca2^p gene (Gardner et al. 1992, Lyon et al. 1992); thus, the molecular nature of the defect is unknown. Oca2^p-d/Oca2^p-25H compound heterozygotes have a color phenotype intermediate between those of the two homozygotes: eyes are "lighter at birth than those of Oca2^p-d/Oca2^p-d mice (but not as light as those of Oca2^p/Oca2^p mice) and darken by weaning"; ears and tail are lighter than those of Oca2^p-d/Oca2^p-d mice, but coat color is indistinguishable. The compound heterozygotes exhibit no behavioral abnormalities and are fertile (Lyon et al. 1992).

Development

Both the Oca2^p-d and Oca2^p-25H mutations were radiation induced at the Medical Research Council Radiobiology Unit, Harwell, UK, the former by X-irradiation of the fetus and the latter by neutron irradiation of a male mouse, both of strains/stocks of unidentified lineage.

Allele

Symbol: Oca2^p-d
Name: dark pink-eyed
MGI accession ID: MGI:1856117
Generation method: Radiation induced
Synonyms: p^d
Marker symbol: Oca2
Marker name: oculocutaneous albinism II
Marker synonyms: BEY; BEY1; BEY2; BOCA; D15S12; D7H15S12; EYCL; EYCL2; EYCL3; HCL3; P; PED; SHEP1
Chromosome: 7
Strain of origin: Not Specified
General note: The molecular basis for this mutant allele has not been determined.

Allele

Symbol: Oca2^p-25H
Name: pink-eyed dilution 25 Harwell
MGI accession ID: MGI:1856126
Generation method: Radiation induced
Synonyms: Herc2^p-25H; p^25H
Marker symbol: Oca2
Marker name: oculocutaneous albinism II
Marker synonyms: BEY; BEY1; BEY2; BOCA; D15S12; D7H15S12; EYCL; EYCL2; EYCL3; HCL3; P; PED; SHEP1
Chromosome: 7
Strain of origin: Not Specified
Molecular note: Southern blot analyses using cDNA probes from the pink-eyed dilution locus show that this allele comprises an inversion of a segment of Chromsome 7 that alters the 5'end of the Oca2^p gene preventing transcription of p.
General note: p^25H, p-25 Harwell, recessive. This allele was neutron-irradiation-induced. Homozygotes are very similar to p^6H homozygotes, except that sperm morphology differs; p^25H homozygous males have a lower proportion of normal sperm (J:5219, J:5501, J:15082, J:5808). The sperm shows a loss of negative charge along the whole length of the tail (defined by the inability to stain with the positively charged colloidal iron hydroxide), suggesting that the defect in spermatogenesis may involve the Golgi apparatus and/or plasma membrane (J:11957). Females have reduced fertility. In addition, in p^25H homozygotes of both sexes, the pars nervosa of the pituitary contains degenerating nerve axons (J:5508), and the hypothalamus has reduced binding capacity for estradiol-17ß (J:5219). Mutant females can generally produce a small, first litter, but the pups often die neonatally due to poor maternal behavior, which may involve improper nesting (J:49046).