MAMMALIAN HOMOLOG OF DROSOPHILA-RETINAL-DEGENERATION-B RESCUES THE MUTANT FLY PHENOTYPE

Mutations in the Drosophila rdgB gene, which encodes a transmembrane p hosphatidylinositol transfer protein (PITP), cause a light-enhanced re tinal degeneration. Cloning of mammalian rdgB orthologs (mrdgB) reveal predicted proteins that are 39% identical to rdgB, with highest homol ogy in the N-terminal PITP domain (62%) and in a region near the C ter minus (65%). The human mrdgB gene spans similar to 12 kb and maps to 1 1q13.1, a locus where several retinal diseases have also been mapped. Murine mrdgB maps to a syntenic region on the proximal region of chrom osome 19. MrdgB is specifically expressed in the retina and brain. In the retina, MrdgB protein is localized to photoreceptor inner segments and the outer and inner plexiform layers. Expression of murine mrdgB in mutant flies fully rescues both the rdgB-dependent retinal degenera tion and abnormal electroretinogram. These results suggest the existen ce of similarities between the invertebrate and mammalian retina that were not previously appreciated and also identify mrdgB as a candidate gene for retinal diseases that map to 11q13.1.