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

Nature. 1993 Jan 7;361(6407):72-6. doi: 10.1038/361072a0.

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).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Albinism, Oculocutaneous / genetics*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Blotting, Southern
  • Carrier Proteins*
  • Chromosome Deletion
  • Chromosomes, Human, Pair 15
  • Crosses, Genetic
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Membrane Transport Proteins*
  • Mice
  • Mice, Inbred Strains
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Prader-Willi Syndrome / genetics

Substances

  • Carrier Proteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • OCA2 protein, human
  • P protein, mouse

Associated data

  • GENBANK/M99564