Characterization of the murine gene corresponding to human Hermansky-Pudlak syndrome type 3: Exclusion of the subtle gray (sut) locus

Hermansky-Pudlak syndrome (HPS) consists of oculocutaneous albinism and a b leeding diathesis due to absent platelet dense bodies. In addition to exhib iting considerable phenotypic variation, this autosomal recessive disorder displays locus heterogeneity. One causative gene is HPS1, coding for a prot ein of unknown function and resulting in HPS-1 disease, common in northwest Puerto Rico. A second HPS-causing gene is ADTB3A, coding for the beta 3A s ubunit of adaptor complex-3 (AP-3, a coat protein complex) and resulting in HPS-2 disease. Each of these HPS subtypes has a murine counterpart, specif ically pale ear for HPS-1 and pearl for HPS-2. Recently, the HPS3 gene, res ponsible for HPS-3 disease in a genetic isolate of central Puerto Rico, was isolated and characterized. Its location on human chromosome 3q24 suggeste d that the mouse model corresponding to HPS-3 disease might be subtle gray. To examine this possibility, we determined the mouse HPS3 sequence, its ge nomic organization, and its amino acid sequence, which shares 95.8% identit y with the human protein. We demonstrated that the subtle gray mouse produc es a normal size and amount of HPS3 mRNA and has an entirely normal sequenc e in every exon and intron/exon boundary. Furthermore, subtle gray exhibits a normal contingent of platelet dense bodies. Together, these data elimina te subtle gray as a murine model for HPS-3 disease and suggest that other m ouse models be examined. (C) 2001 Academic Press.