A gene for the mouse pink-eyed dilution locus and for human type II oculocutaneous albinism

Abstract

The mouse pink-eyed dilution (p) locus on chromosome 7 is associated with defects of skin, eye and coat pigmentation. Mutations at p cause a reduction of eumelanin (black-brown) pigment and altered morphology of black pigment granules (eumelanosomes), but have little effect on pheomelanin (yellow-red) pigment. We show here that the human complementary DNA DN10, linked to the p locus in mice, identifies the human homologue (P) of the mouse p gene, and appears to encode an integral membrane transporter protein. The expression pattern of this gene in various p mutant mice correlates with the pigmentation phenotype; moreover, an abnormally sized messenger RNA is detected in one mutant, p(un), which reverts to the normal size in p(un) revertants. The human P gene corresponds to the D15S12 locus within the chromosome segment 15q11-q13, which is typically deleted in patients with Prader-Willi and Angelman syndrome (see ref. 5 for review). These disorders are phenotypically distinct, depending on the parent of origin of the deleted chromosome, but both syndromes are often associated with hypopigmentation of the skin, hair and eyes (see ref. 8 for review), and deletion of the P gene may be responsible for this hypopigmentation. In addition, we report a mutation in both copies of the human P gene in one case of tyrosinase-positive (type II) oculocutaneous albinism, recently linked to 15q11-q13 (ref. 9).

Angelman syndrome: a review of clinical and genetic aspects

“…The locus for the P gene which is implicated in type II oculocutaneous albinism also lies within this region. 77 Recent studies have shown that AS deletion patients with hypopigmentation frequently have a mutation of the P gene on the remaining chromosomal homologue 78 79 and some patients have the characteristic ocular findings of albinism with misrouting of optic nerve fibres at the optic chiasm. 80 Patients with uniparental disomy of chromosome 15 have a low incidence of seizures, microcephaly, and hypopigmentation.…”

Inheritance of a novel mutated allele of the OCA2 gene associated with high incidence of oculocutaneous albinism in a Polynesian community

“…9 However, the highest incidence of OCA2 so far molecularly characterized at slightly o1:2000 is in the Native American Navajos with a carrier frequency of 4.5%, estimated to originate from a single founder. 10 The OCA2 locus maps to chromosome 15q11.2-q12 11 and is the human homolog of the mouse pink-eyed dilution gene (p) 12,13 encoding the P-protein. Structurally, the 838 amino-acid P-protein is predicted to contain 12 transmembrane-spanning domains.…”

Pink-eyed Dilution Protein Controls the Processing of Tyrosinase

“…In contrast to oculocutaneous albinism type 1, which results from Tyr mutations, patients with OCA2 express active TYR (King et al, 1985). p was initially thought to be a melanosomal tyrosine transporter (Kugelman and Van Scott, 1968;Rinchik et al, 1993;Lee et al, 1995;Sviderskaya et al, 1997;Rosemblat et al, 1998). However, kinetic studies of tyrosine uptake showed that there was a functional tyrosine transporter system in melanosomes of p-null melanocytes, and no difference in the rate of tyrosine uptake was found between wild-type and p-null melanocytes (Gahl et al, 1995;Potterf et al, 1998).…”