Biomedical subjects

Ming-Cai Zhang

Publications and source records attributed to Ming-Cai Zhang.

3 recordsLinked to original sources

PubMed2006

A non-major histocompatibility locus determines tissue specificity in the pathogenic process underlying synovial proliferation in a mouse arthropathy model.

BACKGROUND: The incidence and characteristics of spontaneous ankylosis in the ankle of specific F(1) mice descended from two Fas-deficient strains were reported. Here the coincidence of synovial proliferation and ankylosis in the descendent F(2) mice is reported. AIM: To clarify whether the two distinct manifestations are genetically different. METHODS: An arthropathic group of mice (MCF(2)) were bred by intercrossing MRL/Mp.Fas(lpr)-sap(-)/sap(-) and C3H/He.Fas(lpr) mice. All mice were killed by bleeding under anaesthesia when they were 6 months old. Pathological grades for synovial proliferation were determined by microscopical examination. To obtain a linkage locus, the whole genome of male MCF(2) mice was scanned by using 73 microsatellite markers. RESULTS: Synovial proliferation was equally observed in male and female MCF(2) mice. No correlation was observed between the grades of synovial proliferation and the ankylosis occurring in the MCF(2) mice. A suggestive susceptibility locus was shown in the middle of chromosome 11. This locus was an MRL allele with a recessive inheritance mode. CONCLUSION: The pathogenic mechanisms of synovial proliferation and ankylosis are genetically different. The present locus is overlapped with some loci associated with rheumatoid arthritis and with others associated with experimental arthritides.

Animals↗

PubMed2006

A signal adaptor SLAM-associated protein regulates spontaneous autoimmunity and Fas-dependent lymphoproliferation in MRL-Faslpr lupus mice.

Autoantibody production and lymphadenopathy are common features of systemic autoimmune disease. Targeted or spontaneous mutations in the mouse germline have generated many autoimmune models with these features. Importantly, the models have provided evidence for the gene function in prevention of autoimmunity, suggesting an indispensable role for the gene in normal immune response and homeostasis. We describe here pathological and genetic characterizations of a new mutant strain of mice, the mutation of which spontaneously occurred in the Fas-deficient strain, MRL/Mp.Faslpr (MRL/lpr). MRL/lpr is known to stably exhibit systemic lupus erythematosus-like diseases. However, the mutant mice barely displayed autoimmune phenotypes, though the original defect in Fas expression was unchanged. Linkage analysis using (mutant MRL/lpr x C3H/lpr)F2 mice demonstrated a nucleotide insertion that caused loss of expression of small adaptor protein, signaling lymphocyte activation molecule (SLAM)-associated protein (SAP). SAP is known to be a downstream molecule of SLAM family receptors and to mediate the activation signal for tyrosine kinase Fyn. Recent studies have shown pleiotropic roles of SAP in T, B, and NK cell activations and NKT cell development. The present study will provide evidence for an essential role for SAP in the development of autoimmune diseases, autoantibodies, and lymphadenopathy in MRL/lpr lupus mice.

Amino Acid Sequence↗

PubMed2005

Implication of allelic polymorphism of osteopontin in the development of lupus nephritis in MRL/lpr mice.

Potentially, autoimmune diseases develop from a combination of multiple genes with allelic polymorphisms. An MRL/Mp-Fas(lpr) (/) (lpr) (MRL/lpr) strain of mice develops autoimmune diseases, including lupus nephritis, but another lpr strain, C3H/HeJ-Fas(lpr) (/) (lpr) (C3H/lpr) does not. This indicates that MRL polymorphic genes are involved in the development of the diseases. By quantitative trait loci (QTL) analysis using 527 of the (MRL/lpr x C3H/lpr)F(2) mice, we identified a novel locus for susceptibility to lupus nephritis at map position D5Mit115 on chromosome 5, the same alias of the osteopontin (Opn) gene (LOD score =4.0), susceptible in the MRL allele. In functional analyses of the MRL and C3H Opn alleles using synthetic osteopontin (OPN) made with a new method "cell-free system" with wheat germ ribosomes, the MRL-OPN induced higher expression and production of immunoglobulins as well as cytokines including TNF-alpha, IL-1beta and IFN-gamma in splenocytes and/or macrophages than that of the C3H allele. These findings suggest that allelic polymorphism of OPN causes the functional differences in antibody production and macrophage activation between MRL and C3H strains, possibly involved in the development of lupus nephritis.

Alleles↗