Transcriptomics

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Cell cyclin kinase inhibitor Cdkn2c regulates B cell homeostasis and function in the NZM2410-derived murine lupus susceptibility locus Sle2c1


ABSTRACT: Sle2c1 is an NZM2410-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. Here we showed that expression of Sle2c1 enhances NZB cellular phenotypes that have been associated with autoimmune pathogenesis. A combination of genetic mapping and candidate gene analysis presents Cdkn2c, a gene encoding for cyclin kinase inhibitor p18INK4c (p18), as the top candidate gene for inducing the Slec2c1 associated expansion of B1a cells. A novel SNP in the Cdkn2c promoter is associated with a significantly reduced Cdkn2c expression in the splenic B cells and B1a cells from Sle2c1-carrying mice, which leads to defective G1 cell cycle arrest in splenic B cells and increased proliferation of Pc B1a cells. As cell cycle is differentially regulated in B1a and B2 cells, these results suggest that Cdkn2c play a critical role in B1a cell self renewal, and that its impaired expression leads to an accumulation of these cells with high autoreactive potential. Total RNA from peritoneal cavity B cells (B1a) and splenic B cells (Bs) was isolated, with 4 biological replicates each. Gene expression data from C57BL/6 mice were compared with data from B6.Sle2c1 mice.

ORGANISM(S): Mus musculus  

SUBMITTER: Anusha Vallurupalli   Igor M Dozmorov  Daniel Perry  Henry Baker  Laurence Morel  Zhiwei Xu  Hari-Hara S Potula  Igor Dozmorov 

PROVIDER: E-GEOD-23114 | ArrayExpress | 2010-07-24

SECONDARY ACCESSION(S): GSE23114PRJNA131501

REPOSITORIES: GEO, ArrayExpress

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