Source:http://linkedlifedata.com/resource/pubmed/id/21543644
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
2011-6-7
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pubmed:abstractText |
Sle2c1 is an NZM2410- and NZB-derived lupus susceptibility locus that induces an expansion of the B1a cell compartment. B1a cells have a repertoire enriched for autoreactivity, and an expansion of this B cell subset occurs in several mouse models of lupus. A combination of genetic mapping and candidate gene analysis presents Cdkn2c, a gene encoding for cyclin-dependent kinase inhibitor p18(INK4c) (p18), as the top candidate gene for inducing the Slec2c1-associated expansion of B1a cells. A novel single nucleotide polymorphism in the NZB allele of the Cdkn2c promoter is associated with a significantly reduced Cdkn2c expression in the splenic B cells and peritoneal cavity B1a cells from Sle2c1-carrying mice, which leads to a defective G1 cell cycle arrest in splenic B cells and increased proliferation of peritoneal cavity B1a cells. As the cell cycle is differentially regulated in B1a and B2 cells, these results suggest that Cdkn2c plays a critical role in B1a cell self-renewal and that its impaired expression leads to an accumulation of these cells with high autoreactive potential.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1550-6606
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
186
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6673-82
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pubmed:meshHeading |
pubmed-meshheading:21543644-Animals,
pubmed-meshheading:21543644-Autoimmunity,
pubmed-meshheading:21543644-B-Lymphocyte Subsets,
pubmed-meshheading:21543644-B-Lymphocytes,
pubmed-meshheading:21543644-Cell Cycle,
pubmed-meshheading:21543644-Cell Proliferation,
pubmed-meshheading:21543644-Chromosome Mapping,
pubmed-meshheading:21543644-Cyclin-Dependent Kinase Inhibitor p18,
pubmed-meshheading:21543644-Disease Models, Animal,
pubmed-meshheading:21543644-Genetic Loci,
pubmed-meshheading:21543644-Genetic Predisposition to Disease,
pubmed-meshheading:21543644-Homeostasis,
pubmed-meshheading:21543644-Lupus Erythematosus, Systemic,
pubmed-meshheading:21543644-Lymphocyte Count,
pubmed-meshheading:21543644-Mice,
pubmed-meshheading:21543644-Polymorphism, Single Nucleotide
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pubmed:year |
2011
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pubmed:articleTitle |
Cyclin-dependent kinase inhibitor Cdkn2c regulates B cell homeostasis and function in the NZM2410-derived murine lupus susceptibility locus Sle2c1.
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pubmed:affiliation |
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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