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Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14560-5. doi: 10.1073/pnas.1111056108. Epub 2011 Aug 12.

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

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1
Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.

Abstract

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.

PMID:
21841138
PMCID:
PMC3167509
DOI:
10.1073/pnas.1111056108
[Indexed for MEDLINE]
Free PMC Article
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