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| Status |
Public on Jul 24, 2010 |
| Title |
Cell cyclin kinase inhibitor Cdkn2c regulates B cell homeostasis and function in the NZM2410-derived murine lupus susceptibility locus Sle2c1 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
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.
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| Contributor(s) |
Xu Z, Potula HS, Vallurupalli A, Perry D, Baker H, Dozmorov I, Morel L |
| Citation(s) |
21543644 |
| |
| Submission date |
Jul 23, 2010 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Igor M Dozmorov |
| E-mail(s) |
igor-dozmorov@omrf.org
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| Phone |
405-271-7052
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| Fax |
405-271-7063
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| URL |
http://omrf.org
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| Organization name |
OMRF
|
| Department |
Arthritis & Immunology
|
| Street address |
825 NE 13th Street
|
| City |
Oklahoma City |
| State/province |
OK |
| ZIP/Postal code |
73162 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA131501 |
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