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Publication : A targeted mutation in the IL-4Ralpha gene protects mice against autoimmune diabetes.

First Author  Radu DL Year  2000
Journal  Proc Natl Acad Sci U S A Volume  97
Issue  23 Pages  12700-4
PubMed ID  11050183 Mgi Jnum  J:65807
Mgi Id  MGI:1927320 Doi  10.1073/pnas.230431397
Citation  Radu DL, et al. (2000) A targeted mutation in the IL-4Ralpha gene protects mice against autoimmune diabetes. Proc Natl Acad Sci U S A 97(23):12700-4
abstractText  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.
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