Abstract

Normal platelet production and platelet function are critical to the maintenance of vascular integrity. Abnormalities in these processes contribute to several important inherited and acquired platelet disorders such as thrombocytopenia and platelet storage pool disease (SPD). Recent studies indicate that (a) inherited thrombocytopenia due to lowered rates of platelet production is common in humans and (b) that SPD is a very common cause of inherited prolonged bleeding in humans. Current treatment of these disorders by platelet transfusions contains a risk of transmission of blood borne infectious diseases and of alloimmunization of patients. Nevertheless, knowledge of genes regulating platelet production and platelet of SPD is very limited.
The specific Aims are to: 1) identify and partially characterize the gm gene by a positional cloning approach; 2) simultaneously approach the identification and partial characterization of the gm gene by a candidate gene approach; and 3)initiate studies to identify the sdy gene by a positional candidate approach. Molecular markers located within 0.3 centiMorgans (3 X 105 base and pairs) of the gm and sdy genes will be identified by comparing the segregation of each gene and microsatellite and/or CDNA markers in interspecific mouse backcrosses.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL051480-01A2
Application #
2228269
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1995-08-01
Project End
2000-06-30
Budget Start
1995-08-01
Budget End
1996-06-30
Support Year
1
Fiscal Year
1995
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

Chintala, Sreenivasulu; Novak, Edward K; Spernyak, Joseph A et al. (2009) The Vps33a gene regulates behavior and cerebellar Purkinje cell number. Brain Res 1266:18-28
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

Showing the most recent 10 out of 32 publications