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-beta (TGF-beta) mRNA and that lungs of TSK/+, IL-4-/- mice had substantially less TGF-beta mRNA than lungs of TSK/+, IL-4+/+ mice. Thus IL-4 seems to regulate the expression of TGF-beta in fibroblasts, providing an explanation for the absence of cutaneous hyperplasia in TSK/+, IL-4Ralpha-/- and TSK/+, TGF-beta+/- mice.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Collagen / biosynthesis
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Crosses, Genetic
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Embryo Loss / genetics*
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Embryo Loss / metabolism
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Female
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Fibroblasts / metabolism*
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Fibroblasts / pathology
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Gene Deletion
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Gene Expression Regulation
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Half-Life
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Homozygote*
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Interleukin-4 / deficiency*
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Interleukin-4 / genetics
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Interleukin-4 / metabolism
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Lung / metabolism
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Lung / pathology
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Male
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Mice
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Mice, Inbred Strains
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Mutation / genetics*
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Phenotype
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Pulmonary Emphysema / genetics
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Pulmonary Emphysema / metabolism
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Pulmonary Emphysema / pathology
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RNA Stability
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Skin / metabolism
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Skin / pathology*
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Suppression, Genetic / genetics
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Survival Rate
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism*
Substances
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RNA, Messenger
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Transforming Growth Factor beta
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Interleukin-4
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Collagen