Source:http://linkedlifedata.com/resource/pubmed/id/10655061
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2000-2-28
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| pubmed:abstractText |
The c-kit-encoded transmembrane tyrosine kinase receptor for stem cell factor (Kit/SCF-R) is required for normal haematopoiesis, melanogenesis and gametogenesis. However, the roles of individual Kit/SCF-R-induced signalling pathways in the control of developmental processes in the intact animal are completely unknown. To examine the function of SCF-induced phosphatidylinositol (PI) 3'-kinase activation in vivo, we employed the Cre-loxP system to mutate the codon for Tyr719, the PI 3'-kinase binding site in Kit/SCF-R, to Phe in the genome of mice by homologous recombination. Homozygous (Y719F/Y719F) mutant mice are viable. The mutation completely disrupted PI 3'-kinase binding to Kit/SCF-R and reduced SCF-induced PI 3'-kinase-dependent activation of Akt by 90%. The mutation induced a gender- and tissue-specific defect. Although there are no haematopoietic or pigmentation defects in homozygous mutant mice, males are sterile due to a block in spermatogenesis, with initially decreased proliferation and subsequent extensive apoptosis occurring at the spermatogonial stem-cell level. In contrast, female homozygotes are fully fertile. This is the first report so far demonstrating the role of an individual signalling pathway downstream of Kit/SCF-R in the intact animal. It provides the first in vivo model for male sterility caused by a discrete signalling pathway defect affecting early germ cells.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
|
| pubmed:issn |
1061-4036
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
24
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
157-62
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:10655061-Amino Acid Substitution,
pubmed-meshheading:10655061-Animals,
pubmed-meshheading:10655061-Apoptosis,
pubmed-meshheading:10655061-Codon,
pubmed-meshheading:10655061-Embryonic and Fetal Development,
pubmed-meshheading:10655061-Enzyme Activation,
pubmed-meshheading:10655061-Exons,
pubmed-meshheading:10655061-Female,
pubmed-meshheading:10655061-Fertility,
pubmed-meshheading:10655061-Genomic Library,
pubmed-meshheading:10655061-Heterozygote,
pubmed-meshheading:10655061-Homozygote,
pubmed-meshheading:10655061-Introns,
pubmed-meshheading:10655061-Male,
pubmed-meshheading:10655061-Mice,
pubmed-meshheading:10655061-Mice, Mutant Strains,
pubmed-meshheading:10655061-Mutagenesis, Site-Directed,
pubmed-meshheading:10655061-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:10655061-Proto-Oncogene Proteins c-kit,
pubmed-meshheading:10655061-Signal Transduction,
pubmed-meshheading:10655061-Stem Cell Factor
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| pubmed:year |
2000
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| pubmed:articleTitle |
Kit/stem cell factor receptor-induced activation of phosphatidylinositol 3'-kinase is essential for male fertility.
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| pubmed:affiliation |
Molecular Biology and Virology Laboratory, The Salk Institute, La Jolla, California, USA. blume@salk.edu
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|