ISOLATION AND CHARACTERIZATION OF A MOUSE HOMOLOG OF THE X-LINKED OCULAR ALBINISM (OA1) GENE

Ocular albinism type 1 (OA1) is an X-linked human genetic disorder tha t affects retinal pigment cells and, to a lesser degree, neural crest- derived melanocytes. The OA1 gene is located close to the pseudoautoso mal region and predicts a novel protein whose function is unknown. How ever, histologic studies of affected patients have suggested a potenti al role in melanosome biogenesis. Here we report the isolation and cha racterization of the mouse homolog of the human OA1 gene, termed Moa1. Two Moa1 isoforms were isolated from a melanoma cDNA library and pred icted to encode proteins of 405 and 249 amino acids with six and two t ransmembrane-spanning regions, respectively. Interspecific backcross m apping yielded a map order and distances (cM) of cen-Moal-3.1 +/- 1.8- Piga-2.1 +/- 1.5-Amel, indicating that Moa1 is located much farther aw ay from the pseudoautosomal region than its human homolog. In adult ti ssues, both Moa1 isoforms were detected in the eye by Northern hybridi zation. In neonatal tissues, Moa1 RNA was detected in both skin and ey es by Northern hybridization and was not affected by the absence of pi gment in mice carrying the albino mutation, or by the type of pigment synthesized, i.e., eumelanin vs pheomelanin, in mice carrying the blac k-and-tan mutation. Expression of Moa1 RNA was not detected in embryon ic tissues by Northern analysis or by in situ hybridization despite th e active synthesis of ocular pigment by E16.5. These results provide i nsight into the structure and possible function of the OA1 protein and suggest a more complex relationship between the human and mouse X chr omosomes than was previously thought to exist. (C) 1996 Academic Press , Inc.