The inherited human syndromes of oculocutaneous albinism and in particular the subform termed Hermansky Pudlak Syndrome (HPS) cause considerable morbidity and mortality, yet knowledge of the genes which cause the syndrome and efficacious treatments are minimal. In contrast, studies in the mouse have identified at least 14 different genes which directly cause HPS. The broad long-term objective of this research is to utilize the genetic advantages of the mouse to clone and characterize the mouse HPS and corresponding human homologs to better understand the causes and ultimately devise therapies for severe forms of human HPS. In particular, it is proposed to clone and partially characterize one of the more defined mouse HPS genes, ruby eye. The ruby eye gene has intrinsic interest, not only because it causes HPS, but also because it regulates the biogenesis/processing/secretion of three subcellular organelles; melanosomes, lysosomes and platelet dense granules.
The specific aims of the proposal are to: (1) identify the mouse ruby eye (ru) gene by positional/candidate gene approaches; (2) isolate the human homolog corresponding to the ruby eye cDNA and test for alteration in this gene in HPS kindreds; and (3) partially characterize the expression and regulation of the mouse ruby eye gene.
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