动物造模,系统性红斑狼疮自发动物模型 z-bio 2023-10-09 1255

　　1. NZB/W F1 This model is the earliest and most classic, which produces NZB/W F1 generations through hybridization between (New Zealand mouse black strain) (NZB) and (New Zealand mouse white strain) (NZW). F1 generations can develop into highly similar severe lupus like phenotypes. This phenotype includes lymph node disease, splenomegaly, elevated serum ANA (including anti ds-DNA antibodies), and immune complex mediated lupus nephritis. The above manifestations can occur in animals at the 5th to 6th months of the disease course, while renal failure and death may occur at the 10th to 12th months. In addition, female mice develop diseases earlier and more severely than male mice, and produce antibodies such as dsDNA with higher titers. Histopathology shows chronic glomerulonephritis with severe mesangial hyperplasia and crescent formation. This model also has some shortcomings, such as the inability to produce anti RNA complex antibodies; Female mice in the F1 generation may experience estrogen bias, and ovariectomy only delays the onset of the disease and lowers the antibody titer.

　　2. MRL/lpr This strain is a hybrid of LG/J, C3H/Di, C57BL/6, and AKR/J mice, and its genes are mainly derived from LG/J mice. This model has a defect in the expression of Fas receptor molecules due to a hidden mutation in lpr (lymphoproliferative lymphoid tissue) on chromosome 19. Due to the accumulation of CD4 and CD8 double negative cells and B220+T cells, lymph node disease exhibits SLE like phenotype characteristics. This model has no gender difference in onset and can have high concentrations of circulating immunoglobulins such as ANA, anti ssDNA, anti ds-DNA, anti Sm, and rheumatoid factors. Renal damage is subacute proliferative glomerulonephritis, with mild to moderate proteinuria, and a 50% mortality rate occurring at the 5th month. Pathological changes begin to appear in mice at around 12 weeks of age, and vasculitis and kidney damage occur at 15-20 weeks of age. The renal pathological manifestations are similar to human lupus nephritis, characterized by infiltration of inflammatory cells, vasculitis, mesangial cell proliferation, and interstitial tubular lesions. Most of them die from glomerulonephritis at 5-7 months of age.

　　3. SXSB/Yaa SXSB mice were obtained by backcrossing F1 male mice with SB/Le through C57BL6/J and SB/Le hybridization. The mice exhibited 100% lupus like disease, and the male mice developed earlier and more severe disease due to carrying the Yaa gene (Y-chromosome autoimmune acceleration factor) on the Y chromosome. This disease model can exhibit secondary lymphoid tissue proliferation, immune complex mediated glomerulonephritis, monocytosis, hypergammaglobulinemia, antinuclear antibodies, anti red blood cell autoantibodies, and high serum retroviral glycoprotein gp70 titers. The average survival time for males is 5 months, while for females it is 14 months. The main cause of death is proliferative glomerulonephritis.