[Polymorphism of T cell receptor genes and hyper-production of cytokines: their possible contribution to the pathogenesis of IgA nephropathy in ddY mouse].
The ddY mouse has been used as the spontaneous model animal of human IgA nephropathy (IgAN), because kidney lesion as well as immunological abnormalities resemble that of human IgAN. The intensity of mesangial IgA deposition in neonatally thymectomized ddY mice, in which T cell function was impaired, was less severe, indicating that cytokines from T cells determine the amount of mesangial IgA deposition. Therefore ddY mouse may possess a large amount of cytokines due to hyperactivity of T cells. To elucidate the reason for T cell hyperactivity in ddY mice, genetic polymorphism of T cell receptor genes was examined. Though restriction fragment length polymorphism (RFLP) of alpha and beta chain genes is the same as that of normal mice, the RFLP of the gamma chain is unique. Since T cells bearing gamma chain are observed frequently in the tonsil gland or intestinal intraepithelium, which are indispensable lymphoid tissues for IgA production, an uncommon DNA sequence of the gamma chain could contribute to the pathogenesis of IgAN.
Department of Internal Medicine, Saitama Medical School.
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R
Nagasawa
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T
Takahashi
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T
Mitarai
D000818:Animals; D016207:Cytokines / Q000378:metabolism* / Q000502:physiology; D004195:Disease Models, Animal; D005920:Glomerular Mesangium / Q000378:metabolism; D005922:Glomerulonephritis, IGA / Q000209:etiology* / Q000235:genetics; D007070:Immunoglobulin A / Q000378:metabolism; D051379:Mice; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000378:metabolism
D016207:Cytokines; D007070:Immunoglobulin A; D011948:Receptors, Antigen, T-Cell