Regenerative phenotype in mice with a point mutation in transforming growth factor β type I receptor (TGFBR1)

Liu J.; Johnson K.; Li J.Piamonte V.Steffy B.M.Hsieh M.H.Ng N.Zhang J.Walker J.R.Ding S.Muneoka K.Wu X.Glynne R.Schultz P.G.

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Regenerative phenotype in mice with a point mutation in transforming growth factor β type I receptor (TGFBR1)

机译：Regenerative phenotype in mice with a point mutation in transforming growth factor β type I receptor (TGFBR1)

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Regeneration of peripheral differentiated tissue in mammals is rare, and regulators of this process are largely unknown. We carried out a forward genetic screen in mice using N-ethyl-N-nitrosourea mutagenesis to identify genetic mutations that affect regenerative healing in vivo. More than 400 pedigrees were screened for closure of a through-and-through punch wound in the mouse ear. This led to the identification of a single pedigree with a heritable, fast, and regenerative wound-healing phenotype. Within 5 wk after ear-punch, a threefold decrease in the diameter of the wound was observed in the mutant mice compared with the wild-type mice. At 22 wk, new cartilage, hair follicles, and sebaceous glands were observed in the newly generated tissue. This trait was mapped to a point mutation in a receptor for TGF-β, TGFBR1. Mouse embryonic fibroblasts from the affected mice had increased expression of a subset of TGF-β target genes, suggesting that the mutation caused partial activation of the receptor. Further, bone marrow stromal cells from the mutant mice more readily differentiated to chondrogenic precursors, providing a plausible explanation for the enhanced development of cartilage islands in the regenerated ears. This mutant mouse strain provides a unique model to further explore regeneration in mammals and, in particular, the role of TGFBR1 in chondrogenesis and regenerative wound healing.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2011年第35期|14560-14565|共6页
作者
Liu J.; Johnson K.; Li J.Piamonte V.Steffy B.M.Hsieh M.H.Ng N.Zhang J.Walker J.R.Ding S.Muneoka K.Wu X.Glynne R.Schultz P.G.;
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作者单位

Department of Chemistry, Skaggs Institute for Chemical Biology, Scripps Research Institute, San Diego, CA 92037, United States;

Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, United States;

Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, United States;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Appendage; Epimorphic; Skin;

Regenerative phenotype in mice with a point mutation in transforming growth factor β type I receptor (TGFBR1)

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