STOCK Oca2^p-J/Oca2^p-bs/J

Stock number: 001584
Research areas: Dermatology Research, Mouse/Human Gene Homologs, Reproductive Biology Research

Description

These mice are heterozygous for two different alleles of oculocutaneous albinism II Oca2^p-J (pink-eyed dilution Jackson) and Oca2^p-bs (pink-eyed dilution black eyed sterile). The compound heterozygotes have a color phenotype intermediate between those of the two homozygotes.

Detailed description

Oca2^p-J/Oca2^p-J mice exhibit significant dilution of coat color with pink eyes, a phenotype similar to that produced by Oca2^p/Oca2^p. The Oca2^p-J mutation is a partial deletion of the gene that completely ablates Oca2^p function (Oakey et al. 1996). Oca2^p-bs/Oca2^p-bs mice show a less extreme coat color dilution and have black eyes from birth; the phenotype of Oca2^p-bs homozygotes also includes stunted growth, jerky gait, male sterility, female semisterility, and impaired maternal behavior, and the smaller-than-expected proportion of Oca2^p-bs homozygous intercross offspring implies reduced prenatal viability (Lyon et al. 1992). The Oca2^p-bs mutation comprises a deletion that begins about 10 kb 5' of the Oca2^p locus and extends for about 8 kb in the proximal direction from it (Lehman et al. 1998). The deletion does not include any part of the transcribed Oca2^p sequence; the hypopigmentation of Oca2^p-bs/Oca2^p-bs mice may be due to a long-distance effect of the deletion or to some other, as yet undefined alteration of the Oca2^p sequence. The non-pigmentation aspects of the Oca2^p-bs phenotype result from the deletion of most of the Herc2 gene (Lehman et al. 1998). Oca2^p-J/Oca2^p-bs compound heterozygotes have a color phenotype intermediate between those of the two homozygotes, exhibit no behavioral abnormalities and are fertile.

Development

The Oca2^p-bs mutation was induced at the Medical Research Council Radiobiology Unit, Harwell, UK by neutron irradiation of a male mouse of unspecified lineage. Oca2^p-J occurred spontaneously in the C3H/HeJ strain at The Jackson Laboratory in 1974.

Allele

Symbol: Oca2^p-bs
Name: pink-eyed dilution black eyed sterile
MGI accession ID: MGI:1856115
Generation method: Radiation induced
Synonyms: Herc2^p-24H; Herc2^p-bs; p^24H; p^bs
Marker symbol: Oca2
Marker name: oculocutaneous albinism II
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 a 5' rearrrangement in the p gene. An intergenic deletion of 960-bp near the carboxy terminus of Herc2 deletes a stretch of 320 amino acids from the predicted protein, including the HECT domain. The overall deletion for this p-region mutant is ~8.0-kb.
General note: p^bs, pink-eyed dilution-black-eyed sterile (formerly p24H); recessive; 960-BP DEL; 320 AA DEL: Arose in descendants of neutron treated mice (J:15082, J:2108). Homozygotes have dark eyes at birth. The coat color in adults is slightly lighter than pd but darker than pdn. At weaning, homozygotes show a slightly jerky behavior (J:15082, J:13043). Males are sterile, with a high proportion of abnormal sperm (multinucleated, multitailed, and acrosomal defects) and a reduced proportion of gonadotropic cells in the pituitary (J:49046, J:5219, 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 greatly reduced fertility, with an increased proportion of polyovular follicles and no corpora lutea (J:5501). 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).

Allele

Symbol: Oca2^p-J
Name: pink-eyed dilution Jackson
MGI accession ID: MGI:1856127
Generation method: Spontaneous
Synonyms: p^J
Marker symbol: Oca2
Marker name: oculocutaneous albinism II
Chromosome: 7
Strain of origin: C3H/HeJ
Molecular note: This allele was shown to be allelic to Oca2^p by a complementation test. Southern blot analysis of Sst1-digested genomic DNA from mice homozygous for this allele, probed with a 1.0-kb DraIII fragment derived from cDNA clone MC2701, revealed deletion of two exon-bearing fragments (6.9 and 10.0 kb) found in wild-type DNA. The deletion has been shown to result in loss from the transcript of 350 base pairs encompassing nucleotides 2195-2545, derived from exons 20-23, and to produce a frameshift resulting in a protein additonally lacking exon 24-encoded amino acids. The missing amino acids include the last part of transmembrane domain 9 and all of transmembrane domains 10-12.