Department of Molecular and Functional Genomics, Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania, USA.
Department of Human Genetics, University of Utah, Salt Lake City, Utah, USA.
Dev Dyn. 2022 Sep;251(9):1613-1627. doi: 10.1002/dvdy.484. Epub 2022 May 20.
The limb phenotypes of Tbx2 and Tbx3 mutants are distinct: loss of Tbx2 results in isolated duplication of digit 4 in the hindlimb while loss of Tbx3 results in anterior polydactyly and posterior oligodactly in the forelimb. In the face of such disparate phenotypes, we sought to determine whether Tbx2 and Tbx3 have functional redundancy during development of the mouse limb. We found that sequential loss of alleles generates defects that are not simply additive of those observed in single mutants and that multiple structures in both the forelimb and hindlimb display compound sensitivity to decreased gene dosage.
Tbx2 和 Tbx3 突变体的肢体表型明显不同：Tbx2 缺失导致后肢的第 4 指单独重复，而 Tbx3 缺失导致前肢的前多趾和后少趾。面对如此不同的表型，我们试图确定 Tbx2 和 Tbx3 在小鼠肢体发育过程中是否具有功能冗余性。我们发现，等位基因的顺序缺失产生的缺陷不是单个突变体中观察到的缺陷的简单累加，并且前肢和后肢的多个结构对基因剂量降低表现出复合敏感性。
