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Publication : Congenic analysis of the NKT cell control gene Nkt2 implicates the peroxisomal protein Pxmp4.

First Author  Fletcher JM Year  2008
Journal  J Immunol Volume  181
Issue  5 Pages  3400-12
PubMed ID  18714012 Mgi Jnum  J:138945
Mgi Id  MGI:3806895 Doi  10.4049/jimmunol.181.5.3400
Citation  Fletcher JM, et al. (2008) Congenic analysis of the NKT cell control gene Nkt2 implicates the peroxisomal protein Pxmp4. J Immunol 181(5):3400-12
abstractText  Type 1 NKT cells play a critical role in controlling the strength and character of adaptive and innate immune responses. We have previously reported deficiencies in the numbers and function of NKT cells in the NOD mouse strain, which is a well-validated model of type 1 diabetes and systemic lupus erythematosus. Genetic control of thymic NKT cell numbers was mapped to two linkage regions: Nkt1 on distal chromosome 1 and Nkt2 on chromosome 2. Herein, we report the production and characterization of a NOD.Nkrp1(b).Nkt2b(b) congenic mouse strain, which has increased thymic and peripheral NKT cells, a decreased incidence of type 1 diabetes, and enhanced cytokine responses in vivo and increased proliferative responses in vitro following challenge with alpha-galactosylceramide. The 19 highly differentially expressed candidate genes within the congenic region identified by microarray expression analyses included Pxmp4. This gene encodes a peroxisome-associated integral membrane protein whose only known binding partner is Pex19, an intracellular chaperone and component of the peroxisomal membrane insertion machinery encoded by a candidate for the NKT cell control gene Nkt1. These findings raise the possibility that peroxisomes play a role in modulating glycolipid availability for CD1d presentation, thereby influencing NKT cell function.
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