| Systemic lupus eiythematosus ( SLE) is a typical multigenic autoimmune disorder with a high incidence, most common in young female. One of its important character is that T and B cells lose the tolerance to autoantigen and produce a variety of autoantibodies. The majority of antibodies directed at nuclear and cy-toplasmic components, with which formed immune complexes and deposited in various tissues causing multiorgan inflammation. Many factors such as genetics, environment, immunity, hormone were concerned with the production of an-toantibody and the pathogenesis of SLE, but genetic factor played a more important role.Along with the immense success of genetic linkage analysis of monogenic diseases, Human Genome Project (HGP) had a promotion to the method of genetic analysis. The cloning of the morbid allele of complex diseases has become the emphasis in genetics study now. Mapping susceptibility allele through characteristic phenotype has been very significant for disclosing the causation of diseases. As autoantibody was an important sign of autoimmune diseases and anti-nuclear antibodies (ANA) made up the majority of antibodies causing LE cell formation, it was one of the first autoantibodies ever detected in SLE. Anti -double - stranded DNA antibodies, with a mean onset 2.2 years before the diagnosis , were found later than antinuclear antibodies. The outbreak of autoimmune diseases in SLE patients and lupus mice was symbolized by the early appearance of ANA, so appearance of these antibodies had crucial effect on the pathogenesis of SLE. Lupus mice could produce antinuclear antibodies spontaneously even in germfree environment, that suggested the exterior factor had less influence in ANA production. ANA also presented in the healthy first - degree relatives ofSLE probands, several studies of concordance rates for SLE in monozygotic had been found up to 92% , that suggested the genetic factor was the mainly reason for the production of ANA in SLE.It was more difficult and could not be repeated easily for genetic linkage study with SLE patients. Mouse studies for genetics had advantages over the linkage studies in human in that it was much simple with congenic mouse strains and backcross progeny and environmental influence was nearly neglected, so it was probable to map susceptibility allele of complex diseases accurately with polymorphic microsatellite markers and quantitative trait locus ( QTL) analysis. In this study, New Zealand Black (NZB) x New Zealand White(NZW)Fl x NZB and ( NZB x NZW) Fl x NZW backcross mice model were set up and polymorphic microsatellite markers and quantitative trait locus (QTL) analysis were used, we separated the susceptibility allele derived from NZB and NZW and analysed genotype of microsatellite in order to map the susceptibility alleles of IgG anti - chromatin antibody, anti - DNA antibody, anti - histone antibody in SLE model - ( NZB x NZW) Fl mice. The study will lay a foundation for cloning and identifying the homologous gene in mankind, therefore provide academic basis to further disclose the pathogenesis of SLE and other autoimmune diseases, and develop new and reliable therapeutic methods.Methods1. Detecting the value of IgG and IgM type anti - chromatin antibody, anti -DNA antibody and anti -histone antibody in serum of NZB, NZW, B/WF1mice aged 8 months with enzyme - linked immunosorbent assay ( ELJSA) , and comparing the level of each antibody in NZB, NZW and B/W Fl mice.2. Breeding backcross mice, sifting through genome database for microsatellite markers wit^ length polymorphism between NZB and NZW. The distance from markers at the two sides of chromosome to the two sides was shorter than 10 centimorgan, and the distance between two markers was shorter than 20 centimo-rgan. Finally the sum of microsatellite DNA genetic markers overlapping 19 chromosome besides sexual chromosome worked out at about 200.3. Genotyping for microsatellite markers; Genomic DNA was extracted from the mouse tail, the polymorphic microsatellites overlapping the whole genome...
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