Disrupting theIL-4gene rescues mice homozygous for the tight-skin mutation from embryonic death and diminishes TGF-β production by fibroblasts
- 12 March 2002
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 99 (6) , 3800-3805
- https://doi.org/10.1073/pnas.052709999
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.Keywords
This publication has 35 references indexed in Scilit:
- Effect of IL-12 Encoding Plasmid Administration on Tight-Skin MouseBiochemical and Biophysical Research Communications, 2001
- Lack of Skin Fibrosis in Tight Skin (TSK) Mice with Targeted Mutation in the Interleukin-4Rα and Transforming Growth Factor-β GenesJournal of Investigative Dermatology, 2001
- A Role for T Helper 2 Cells in Mediating Skin Fibrosis in Tight-Skin MiceCellular Immunology, 1999
- Anti-IL-4 treatment prevents dermal collagen deposition in the tight-skin mouse model of sclerodermaEuropean Journal of Immunology, 1998
- B-cell Deficiency does not Abrogate Development of Cutaneous Hyperplasia in Mice Inheriting the Defective Fibrillin-1 GeneJournal of Autoimmunity, 1997
- A tandem duplication within the fibrillin 1 gene is associated with the mouse tight skin mutation.Genome Research, 1996
- CD4pos, NK1.1pos T cells promptly produce interleukin 4 in response to in vivo challenge with anti-CD3.The Journal of Experimental Medicine, 1994
- Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells.The Journal of Experimental Medicine, 1990
- Delayed-type hypersensitivity to elastase-soluble lung peptides in the tight-skin (Tsk) mouseCellular Immunology, 1983
- Use of a mixture of proteinase-free collagenases for the specific assay of radioactive collagen in the presence of other proteinsBiochemistry, 1971