A Regenerative Trait in Mice with a Point Mutation in TGFBR1

Regeneration of differentiated tissue in mammals is rare. In an effort to identify genes that affect the healing process, we screened G3 mice containing germline point mutations for closure of an ear punch wound. One particular line was identified with a heritable hole closure phenotype containing differentiated tissue. Mapping and sequencing efforts revealed that the mutant mice harbor a R244Q point mutation coded by the TGFBR1 gene which leads to enhanced signaling activity in a reporter gene assay. Although there was no obvious effect on the immune system, bone marrow stromal cells from the mutant mice revealed accelerated chondrogenesis, mimicking the in vivo development of cartilage islands in the regenerated ears. This genetically well-defined mouse model should help to further dissect the role of TGF-beta signaling in vertebrate healing and regeneration.

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Liu J, Johnson K, Li J, Piamonte V, Steffy BM, Hsieh MH, Ng N, Zhang J, Walker JR, Ding S, Muneoka K, Wu X, Glynne R, Schultz PG