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

98 Citations (Scopus)

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

Fingerprint

Transforming Growth Factors
Interleukin-4
Fibroblasts
Skin
Mutation
Genes
Hyperplasia
Lung
Messenger RNA
Emphysema
Gestational Age
Embryonic Structures
Alleles

ASJC Scopus subject areas

  • General

Cite this

Disrupting the IL-4 gene rescues mice homozygous for the tight-skin mutation from embryonic death and diminishes TGF-β production by fibroblasts. / Kodera, Takao; McGaha, Tracy L.; Phelps, Robert; Paul, William E.; Bona, Constantin A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 6, 19.03.2002, p. 3800-3805.

Research output: Contribution to journalArticle

@article{4be2ea23529e45ad8a3c1684ef485887,
title = "Disrupting the IL-4 gene rescues mice homozygous for the tight-skin mutation from embryonic death and diminishes TGF-β production by fibroblasts",
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.",
author = "Takao Kodera and McGaha, {Tracy L.} and Robert Phelps and Paul, {William E.} and Bona, {Constantin A.}",
year = "2002",
month = "3",
day = "19",
doi = "10.1073/pnas.052709999",
language = "English (US)",
volume = "99",
pages = "3800--3805",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "6",

}

TY - JOUR

T1 - Disrupting the IL-4 gene rescues mice homozygous for the tight-skin mutation from embryonic death and diminishes TGF-β production by fibroblasts

AU - Kodera, Takao

AU - McGaha, Tracy L.

AU - Phelps, Robert

AU - Paul, William E.

AU - Bona, Constantin A.

PY - 2002/3/19

Y1 - 2002/3/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0037133611&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037133611&partnerID=8YFLogxK

U2 - 10.1073/pnas.052709999

DO - 10.1073/pnas.052709999

M3 - Article

C2 - 11891315

AN - SCOPUS:0037133611

VL - 99

SP - 3800

EP - 3805

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 6

ER -