Disrupting the IL-4 gene rescues mice homozygous for the tight-skin mutation from embryonic death and diminishes TGF-β production by fibroblasts

Takao Kodera, Tracy L. McGaha, Robert Phelps, William E. Paul, Constantin A. Bona

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

The TSK/TSK mutation is embryonic lethal; embryos have been reported to die at 7-8 days of gestational age. Crossing TSK/+, IL-4+/- mice revealed that disrupting one or both IL-4 alleles allowed survival of 29 and 47%, respectively, of TSK/TSK mice. These mice failed to develop cutaneous hyperplasia but did exhibit the emphysema that is found in TSK/+ mice. We showed that IL-4 stimulation of fibroblasts increased the level of transforming growth factor-β (TGF-β) mRNA and that lungs of TSK/+, IL-4-/-mice had substantially less TGF-β mRNA than lungs of TSK/+, IL-4+/+ mice. Thus IL-4 seems to regulate the expression of TGF-β in fibroblasts, providing an explanation for the absence of cutaneous hyperplasia in TSK/+, IL-4Rα-/- and TSK/+, TGF-β+/-mice.

Original languageEnglish (US)
Pages (from-to)3800-3805
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number6
DOIs
StatePublished - Mar 19 2002

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