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


  • 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-, TGFBR1. Mouse embryonic fibroblasts from the affected mice had increased expression of a subset of TGF- 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.

published proceedings

  • Proc Natl Acad Sci U S A

altmetric score

  • 3.75

author list (cited authors)

  • Liu, J., Johnson, K., Li, J., Piamonte, V., Steffy, B. M., Hsieh, M. H., ... Schultz, P. G.

citation count

  • 32

complete list of authors

  • Liu, Jun||Johnson, Kristen||Li, Jie||Piamonte, Victoria||Steffy, Brian M||Hsieh, Mindy H||Ng, Nicholas||Zhang, Jay||Walker, John R||Ding, Sheng||Muneoka, Ken||Wu, Xu||Glynne, Richard||Schultz, Peter G

publication date

  • August 2011