Disrupting the IL-4 gene rescues mice homozygous for the tight-skin mutation from embryonic death and diminishes TGF-beta production by fibroblasts.
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.
Kodera
Takao
T
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
McGaha
Tracy L
TL
Phelps
Robert
R
Paul
William E
WE
Bona
Constantin A
CA
D000818:Animals; D003094:Collagen / Q000096:biosynthesis; D003433:Crosses, Genetic; D020964:Embryo Loss / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006207:Half-Life; D006720:Homozygote; D015847:Interleukin-4 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011656:Pulmonary Emphysema / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D013489:Suppression, Genetic / Q000235:genetics; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D003094:Collagen