Correlation Engine 2.0
Clear Search sequence regions


Sizes of these terms reflect their relevance to your search.

Systemic lupus erythematosus is considered to be under the control of polygenic inheritance, developing according to the cumulative effects of susceptibility genes with polymorphic alleles; however, the mechanisms underlying the roles of polygenes based on functional and pathological genomics remain uncharacterized. In this study, we substantiate that a CD72 polymorphism in the membrane-distal extracellular domain impacts on both the development of glomerulonephritis and vasculitis in a lupus model strain of mice, MRL/MpJ-Fas(lpr), and the reactivity of BCR signal stimulation. We generated mice carrying a bacterial artificial chromosome transgene originating from C57BL/6 (B6) mice that contains the Cd72(b) locus (Cd72(B6) transgenic [tg]) or the modified Cd72(b) locus with an MRL-derived Cd72(c) allele at the polymorphic region corresponding to the membrane-distal extracellular domain (Cd72(B6/MRL) tg). Cd72(B6) tg mice, but not Cd72(B6/MRL) tg mice, showed a significant reduction in mortality following a marked improvement of disease associated with decreased serum levels of IgG3 and anti-dsDNA Abs. The number of splenic CD4(-)CD8(-) T cells in Cd72(B6) tg mice was decreased significantly in association with a reduced response to B cell receptor signaling. These results indicate that the Cd72 polymorphism affects susceptibility to lupus phenotypes and that novel functional rescue by a bacterial artificial chromosome transgenesis is an efficient approach with wide applications for conducting a genomic analysis of polygene diseases.

Citation

Hisashi Oishi, Takahito Tsubaki, Tatsuhiko Miyazaki, Masao Ono, Masato Nose, Satoru Takahashi. A bacterial artificial chromosome transgene with polymorphic Cd72 inhibits the development of glomerulonephritis and vasculitis in MRL-Faslpr lupus mice. Journal of immunology (Baltimore, Md. : 1950). 2013 Mar 01;190(5):2129-37

Expand section icon Mesh Tags

Expand section icon Substances


PMID: 23365086

View Full Text