Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012104-02
Application #
2888602
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1998-04-01
Project End
2001-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
City
Buffalo
State
NY
Country
United States
Zip Code
14263

  Publications

Guo, Xuemei; Tu, Liyu; Gumper, Iwona et al. (2009) Involvement of vps33a in the fusion of uroplakin-degrading multivesicular bodies with lysosomes. Traffic 10:1350-61
Chintala, Sreenivasulu; Tan, Jian; Gautam, Rashi et al. (2007) The Slc35d3 gene, encoding an orphan nucleotide sugar transporter, regulates platelet-dense granules. Blood 109:1533-40
Gautam, Rashi; Novak, Edward K; Tan, Jian et al. (2006) Interaction of Hermansky-Pudlak Syndrome genes in the regulation of lysosome-related organelles. Traffic 7:779-92
Guttentag, Susan H; Akhtar, Amana; Tao, Jian-Qin et al. (2005) Defective surfactant secretion in a mouse model of Hermansky-Pudlak syndrome. Am J Respir Cell Mol Biol 33:14-21
Chintala, Sreenivasulu; Li, Wei; Lamoreux, M Lynn et al. (2005) Slc7a11 gene controls production of pheomelanin pigment and proliferation of cultured cells. Proc Natl Acad Sci U S A 102:10964-9
Li, Wei; Rusiniak, Michael E; Chintala, Sreenivasulu et al. (2004) Murine Hermansky-Pudlak syndrome genes: regulators of lysosome-related organelles. Bioessays 26:616-28
Gautam, Rashi; Chintala, Sreenivasulu; Li, Wei et al. (2004) The Hermansky-Pudlak syndrome 3 (cocoa) protein is a component of the biogenesis of lysosome-related organelles complex-2 (BLOC-2). J Biol Chem 279:12935-42
Tiwari, Sanjay; Italiano Jr, Joseph E; Barral, Duarte C et al. (2003) A role for Rab27b in NF-E2-dependent pathways of platelet formation. Blood 102:3970-9
Suzuki, Tamio; Oiso, Naoki; Gautam, Rashi et al. (2003) The mouse organellar biogenesis mutant buff results from a mutation in Vps33a, a homologue of yeast vps33 and Drosophila carnation. Proc Natl Acad Sci U S A 100:1146-50
Chiang, Pei-Wen; Oiso, Naoki; Gautam, Rashi et al. (2003) The Hermansky-Pudlak syndrome 1 (HPS1) and HPS4 proteins are components of two complexes, BLOC-3 and BLOC-4, involved in the biogenesis of lysosome-related organelles. J Biol Chem 278:20332-7

Showing the most recent 10 out of 24 publications