Jerome-Majewska Loydie A, Jenkins Gerard P, Ernstoff Elana, Zindy Frederique, Sherr Charles J, Papaioannou Virginia E
Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Dev Dyn. 2005 Dec;234(4):922-33. doi: 10.1002/dvdy.20575.
The closely related T-box genes Tbx2 and Tbx3 are both expressed in the developing mammary glands of mouse embryos and both have been implicated in mammary carcinogenesis. Tbx3 is essential for induction of the mammary placodes in mice. In humans, mutations in TBX3 are responsible for ulnar-mammary syndrome. Here, we show a haploinsufficiency effect of Tbx3 on maintenance of the mammary placodes and on the extent of branching of the ductal tree in mice. Loss or heterozygosity for Tbx2, on the other hand, has no effect on either induction or maintenance of the placodes, although a small effect was seen on branching morphogenesis in adult heterozygotes. However, the deficiency in maintenance of the mammary placodes in Tbx2, Tbx3 double heterozygous mice is more marked than in Tbx3 single heterozygotes, indicating a genetic interaction between the two genes. In spite of a large body of evidence implicating these genes in cell cycle control through the p19(Arf)/p53 pathways, we find no evidence for involvement of these pathways either in embryonic lethality of homozygous mutants or in the mammary gland phenotype of Tbx3 heterozygous mice.
密切相关的T-box基因Tbx2和Tbx3在小鼠胚胎发育中的乳腺中均有表达，且二者都与乳腺癌发生有关。Tbx3对小鼠乳腺基板的诱导至关重要。在人类中，TBX3突变会导致尺骨-乳腺综合征。在此，我们展示了Tbx3对小鼠乳腺基板维持及导管树分支程度的单倍剂量不足效应。另一方面，Tbx2缺失或杂合对基板的诱导或维持均无影响，尽管在成年杂合子中对分支形态发生有轻微影响。然而，Tbx2、Tbx3双杂合小鼠中乳腺基板维持的缺陷比Tbx3单杂合小鼠更明显，表明这两个基因之间存在遗传相互作用。尽管有大量证据表明这些基因通过p19(Arf)/p53途径参与细胞周期调控，但我们没有发现这些途径参与纯合突变体胚胎致死或Tbx3杂合小鼠乳腺表型的证据。
