MOUSE MODELS OF HERMANSKY-PUDLAK-SYNDROME - A REVIEW

Hermansky Pudlak Syndrome (HPS) is a recessively inherited disease aff ecting the contents and/or the secretion of several related subcellula r organelles including melanosomes, lysosomes, and platelet dense gran ules. It presents with disorders of pigmentation, prolonged bleeding, and ceroid deposition, often accompanied by severe fibrotic lung disea se and colitis. In the mouse, the disorder is clearly multigenic, caus ed by at least 14 distinct mutations. Studies on the mouse mutants hav e defined the granule abnormalities of HPS and have shown that the dis ease is associated with a surprising variety of phenotypes affecting m any tissues. This is an exciting time in HPS research because of the r ecent molecular identification of the gene causing a major form of hum an NPS and the expected identifications of several mouse HPS genes. Id entifications of mouse HPS genes are expected to increase our understa nding of intracellular vesicle trafficking, lead to discovery of new h uman HPS genes, and suggest diagnostic and therapeutic approaches towa rd the more severe clinical consequences of the disease.