Albinism is a term used to describe a group of genetic disorders that have in common their reduction of ocular and often cutaneous pigmentation. These disorders can be associated with significant ocular morbidity. The ultimate goal of this research is to understand how mutations at genetic loci that control pigmentation can result in albinism. Four genetic loci known to interact in controlling melanogenesis and to be implicated in various forms of ocular and ocular cutaneous albinism are albino (c), brown (b), slaty (slt), and pink-eyed dilution (p). To accomplish their goals, the applicants propose to combine the power of mouse genetics with techniques of cell and molecular biology and biochemistry. They propose to study eyes and skin from inbred mice of defined genotype, melanocytes cultured from inbred mice, and nonmelanocytic and melanocytic cells of defined genotype transfected with expression vectors encoding specific melanosomal proteins singly and in combination. Chemical crosslinking and the yeast """"""""two hybrid"""""""" system will also be employed to gain further insights into interactions among these melanosomal proteins.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Visual Sciences C Study Section (VISC)
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New York University
Schools of Medicine
New York
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Bowling, Benjamin D; Doudican, Nicole; Manga, Prashiela et al. (2008) Inhibition of mitochondrial protein translation sensitizes melanoma cells to arsenic trioxide cytotoxicity via a reactive oxygen species dependent mechanism. Cancer Chemother Pharmacol 63:37-43
Sone, Michio; Orlow, Seth J (2007) The ocular albinism type 1 gene product, OA1, spans intracellular membranes 7 times. Exp Eye Res 85:806-16
Ni-Komatsu, Li; Orlow, Seth J (2007) Identification of novel pigmentation modulators by chemical genetic screening. J Invest Dermatol 127:1585-92
Ni-Komatsu, Li; Orlow, Seth J (2006) Heterologous expression of tyrosinase recapitulates the misprocessing and mistrafficking in oculocutaneous albinism type 2: effects of altering intracellular pH and pink-eyed dilution gene expression. Exp Eye Res 82:519-28
Staleva, Liliana; Orlow, Seth J (2006) Ocular albinism 1 protein: trafficking and function when expressed in Saccharomyces cerevisiae. Exp Eye Res 82:311-8
Hall, Andrea M; Orlow, Seth J (2005) Degradation of tyrosinase induced by phenylthiourea occurs following Golgi maturation. Pigment Cell Res 18:122-9
Staleva, Liliana; Hall, Andrea; Orlow, Seth J (2004) Oxidative stress activates FUS1 and RLM1 transcription in the yeast Saccharomyces cerevisiae in an oxidant-dependent Manner. Mol Biol Cell 15:5574-82
Hall, Andrea M; Krishnamoorthy, Lalitha; Orlow, Seth J (2004) 25-hydroxycholesterol acts in the Golgi compartment to induce degradation of tyrosinase. Pigment Cell Res 17:396-406
Beermann, Friedrich; Orlow, Seth J; Lamoreux, M Lynn (2004) The Tyr (albino) locus of the laboratory mouse. Mamm Genome 15:749-58
Chen, Kun; Manga, Prashiela; Orlow, Seth J (2002) Pink-eyed dilution protein controls the processing of tyrosinase. Mol Biol Cell 13:1953-64

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