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. Keywords: treatment and time course in wt and mutant samples TGFb or vehicle treatment at different time points in mouse embryonic fibroblasts from wildtype and TGFb1 mutant (heterozygous and homozygous) mice. Mutant is constitutively active.

哺乳动物体内分化组织的再生现象较为罕见。为筛选影响创伤愈合过程的相关基因，本研究对携带生殖系点突变的G3小鼠进行耳穿孔伤口闭合情况的筛选。最终获得一个品系，其呈现可遗传的穿孔闭合表型，且再生组织为分化组织。经定位与测序分析发现，该突变小鼠携带转化生长因子β受体1（TGFBR1）基因编码的R244Q点突变，该突变可在报告基因实验中增强信号通路活性。尽管该突变对免疫系统无明显影响，但突变小鼠的骨髓基质细胞表现出加速的软骨形成过程，模拟了再生耳朵内软骨岛的体内发育进程。该遗传背景清晰的小鼠模型将有助于进一步解析转化生长因子β（TGF-β）信号通路在脊椎动物愈合与再生过程中的作用。关键词：野生型（wt）与突变样本的处理方案及时间进程；对野生型及TGF-β1突变（杂合子与纯合子）小鼠的胚胎成纤维细胞，在不同时间点施以TGF-β或载体对照处理。该突变体为组成型激活型。