Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An MRL/MpJ strain of mice bearing the Fas deletion mutant gene, lpr (MRL/lpr), composed of genomes derived from LG/J, AKR/J, C3H/Di and C57BL/6J mice, develops systemic vasculitis coincidentally with other collagen diseases, but a C3H/HeJ-lpr/lpr (C3H/lpr) strain does not. In a genome-wide screening of the MRL background genes mediating susceptibility to collagen diseases using N2 progeny mice MRL/lpr x (MRL/lpr x C3H/lpr)F1, we previously found that each collagen disease is controlled by a different set of genes. To clarify the candidate genes for vasculitis, we extended the linkage analysis of renal vasculitis to a larger number of N2 mice and to F2 intercross mice. Two distinct recessive susceptibility loci for vasculitis were mapped on chromosome (Chr) 4 at D4Mit89 and D4Mit147 in both progenies. The former was a novel locus for lupus phenotypes, which involved the MRL allele CD72(c) in contrast to the C3H allele CD72(b). The one on Chr 3 was a recessive locus which had an inhibitory effect on vasculitis. From their composition these loci seemed to be derived from AKR/J (for one) and LG/J (for another two) strains, and appeared to act in an additive manner on the development of vasculitis, indicating that vasculitis in MRL/lpr mice is inherited in a polygenic manner.
 ...
PMID:Genetic dissection of vasculitis in MRL/lpr lupus mice: a novel susceptibility locus involving the CD72c allele. 1094 Aug 92

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.
 ...
PMID:A bacterial artificial chromosome transgene with polymorphic Cd72 inhibits the development of glomerulonephritis and vasculitis in MRL-Faslpr lupus mice. 2336 86