Radu D L, Noben-Trauth N, Hu-Li J, Paul W E, Bona C A
Department of Microbiology, Mount Sinai Medical School, New York, NY 10029, USA.
Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12700-4. doi: 10.1073/pnas.230431397.
Autoimmune insulin-dependent diabetes mellitus (IDDM) occurs spontaneously in mice-bearing transgenes encoding the influenza hemagglutinin under the control of the rat insulin promoter and a T cell receptor specific for an hemagglutinin peptide associated with I-E(d). Such "double transgenic" mice expressing wild-type or targeted IL-4Ralpha genes were examined for the onset of IDDM. Eight of 11 mice homozygous for wild-type IL-4Ralpha were hyperglycemic by 8 weeks of age, whereas only 1 of 16 mice homozygous for the targeted allele were hyperglycemic at this time. Most 1L-4Ralpha-/- mice remained normoglycemic to 36 weeks of age. Although only 10% of double transgenic mice homozygous for the wild-type IL-4Ralpha allele survived to 30 weeks, 80% of mice homozygous for the targeted allele did so. Heterozygous mice displayed an intermediate frequency of diabetes. Even as late as 270 days of age, mice homozygous for the targeted allele had no insulitis or only peri-insulitis. Thus, the inability to respond to IL-4 and/or IL-13 protects mice against IDDM in this model of autoimmunity.
自身免疫性胰岛素依赖型糖尿病（IDDM）在携带受大鼠胰岛素启动子控制的编码流感血凝素的转基因以及对与I-E(d)相关的血凝素肽具有特异性的T细胞受体的小鼠中自发发生。对表达野生型或靶向IL-4Rα基因的此类“双转基因”小鼠进行IDDM发病情况检查。11只野生型IL-4Rα纯合小鼠中有8只在8周龄时出现高血糖，而此时16只靶向等位基因纯合小鼠中只有1只出现高血糖。大多数IL-4Rα - / -小鼠到36周龄时仍保持正常血糖水平。虽然野生型IL-4Rα等位基因纯合的双转基因小鼠中只有10%存活到30周，但靶向等位基因纯合的小鼠中有80%存活到了30周。杂合小鼠患糖尿病的频率处于中间水平。即使到270日龄时，靶向等位基因纯合的小鼠也没有胰岛炎或仅有胰岛周围炎。因此，在这种自身免疫模型中，无法对IL-4和/或IL-13作出反应可保护小鼠免受IDDM的影响。
