MOLECULAR CHARACTERIZATION OF TUB, TULP1, AND TULP2, MEMBERS OF THE NOVEL TUBBY GENE FAMILY AND THEIR POSSIBLE RELATION TO OCULAR DISEASES

Tubby, an autosomal recessive mutation, mapping to mouse chromosome 7, was recently found to be the result of a splicing defect in a novel g ene with unknown function, Database searches revealed that sequences c orresponding to the C terminus of the tub protein were highly conserve d across a number of species including humans, mite, Caenorhabditis el egans, Arabidopsis, rice, and maize, and that tub was a member of a ge ne family, We describe here, TUB, the human homolog of mouse tub, and two newly characterized family members, TULP1 for tubby like protein 1 and TULP2. These three faintly members, which differ in the N-termina l half of the protein, share 60-90% amino acid identity across their c onserved C-terminal region and hale distinct tissue expression pattern s. Alternatively spliced transcripts with 5' variable sequences, three of which have been identified for the tubby gene, may mediate tissue specific expression, Wt also report that TUB, TULP1, and TULP2 map to human chromosomes 11p15.4. 6p21.3, and 19q13.1. respectively. TULP1 an d TULP2 map within the minimal intervals identified for retinitis pigm entosa 14 on chromosome 6p21.3 and cone-rod dystrophy on chromosome 19 q13.1. TULP1 and TULP2, which are expressed in the retina, make excell ent candidates for these ocular diseases as a mutation within the tub gene is known to lead to early progressive retinal degeneration.