Linked Life Data

11861280

Source:http://linkedlifedata.com/resource/pubmed/id/11861280

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-2-25
pubmed:abstractText
Hermansky-Pudlak syndrome (HPS) is an inherited hemorrhagic disease affecting the related subcellular organelles platelet dense granules, lysosomes, and melanosomes. The mouse genes for HPS, pale ear and pearl, orthologous to the human HPS1 and HPS2 (ADTB3A) genes, encode a novel protein of unknown function and the beta(3)A subunit of the AP-3 adaptor complex, respectively. To test for in vivo interactions between these genes in the production and function of intracellular organelles, mice doubly homozygous for the 2 mutant genes were produced by appropriate breeding. Cooperation between the 2 genes in melanosome production was evident in increased hypopigmentation of the coat together with dramatic quantitative and qualitative alterations of melanosomes of the retinal pigment epithelium and choroid of double mutant mice. Lysosomal and platelet dense granule abnormalities, including hyposecretion of lysosomal enzymes from kidneys and depression of serotonin concentrations of platelet dense granules were likewise more severe in double than single mutants. Also, lysosomal enzyme concentrations were significantly increased in lungs of double mutant mice. Interaction between the 2 genes was specific in that effects on organelles were confined to melanosomes, lysosomes, and platelet dense granules. Together, the evidence indicates these 2 HPS genes function largely independently at the whole organism level to affect the production and function of all 3 organelles. Further, the increased lysosomal enzyme levels in lung of double mutant mice suggest a cause of a major clinical problem of HPS, lung fibrosis. Finally, doubly mutant HPS mice are a useful laboratory model for analysis of severe HPS phenotypes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1651-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11861280-Adaptor Protein Complex 3, pubmed-meshheading:11861280-Adaptor Protein Complex beta Subunits, pubmed-meshheading:11861280-Animals, pubmed-meshheading:11861280-Blood Platelets, pubmed-meshheading:11861280-Cytoplasmic Granules, pubmed-meshheading:11861280-Cytoplasmic Vesicles, pubmed-meshheading:11861280-Disease Models, Animal, pubmed-meshheading:11861280-Eye, pubmed-meshheading:11861280-Glycoside Hydrolases, pubmed-meshheading:11861280-Lysosomes, pubmed-meshheading:11861280-Melanosomes, pubmed-meshheading:11861280-Membrane Proteins, pubmed-meshheading:11861280-Membrane Transport Proteins, pubmed-meshheading:11861280-Mice, pubmed-meshheading:11861280-Mice, Inbred C57BL, pubmed-meshheading:11861280-Mice, Mutant Strains, pubmed-meshheading:11861280-Pigmentation, pubmed-meshheading:11861280-Proteins, pubmed-meshheading:11861280-Tissue Distribution
pubmed:year
2002
pubmed:articleTitle
The Hermansky-Pudlak syndrome 1 (HPS1) and HPS2 genes independently contribute to the production and function of platelet dense granules, melanosomes, and lysosomes.
pubmed:affiliation
Diabetes Center, Albert Einstein College of Medicine, Bronx, New York, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't