Disrupting the IL-4 gene rescues mice homozygous for the tight-skin mutation from embryonic death and diminishes TGF-β production by fibroblasts
T Kodera, TL McGaha, R Phelps… - Proceedings of the …, 2002 - National Acad Sciences
T Kodera, TL McGaha, R Phelps, WE Paul, CA Bona
Proceedings of the National Academy of Sciences, 2002•National Acad SciencesThe 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 …
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 …
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.
National Acad Sciences