Tbx2-flox Mouse

Tbx2, a member of the T-box family of transcription factors, functions as a transcriptional repressor, mainly mediated by the repression domain in the C-terminal [1]. It is implicated in embryonic development and is involved in multiple pathways. For example, it is a player in the Wnt signaling pathway, and its overexpression can repress the expression of E-cadherin, which is related to epithelial tumor cell invasion. It also interacts with pRb and is involved in the regulation of the p53 pathway [1].

In the developing murine lung, Tbx2 is strongly expressed in mesenchymal progenitors. Genetic lineage tracing with Tbx2cre and the R26mTmG reporter line in mice showed that all fetal smooth muscle cells, endothelial cells and fibroblasts derive from Tbx2+ progenitors. Although the fate of Tbx2-expressing cells is largely independent of Tbx2, a timely down-regulation of Tbx2 is necessary for proper differentiation of bronchial smooth muscle cells and to limit endothelial differentiation [3].

In melanoma, Tbx2 lies downstream from PI3K signaling and binds and is required for the expression of E2F1, a key antisenescence cell cycle regulator. It also interacts with a wide range of transcription factors and co-factors, including components of the BCOR/PRC1.1 complex [2].

In neuroendocrine prostate cancer, Tbx2 drives transdifferentiation through exosome-mediated repression of miR-200c-3p, revealing the Tbx2/miR-200c-3p/SOX2/N-MYC signaling axis [4].

In breast cancer, Tbx2 acts as a transcriptional silencer of tumour suppressor genes like NDRG1 and CST6 through interaction with the CoREST complex to sustain proliferation [5].

In aged rats, Tbx2 knockdown alleviated sevoflurane-induced cognitive disorder and neuron damages by suppressing oxidative stress and ferroptosis, with the BDNF/Nrf2/HO-1 signaling mediating its role [6].

In conclusion, Tbx2 plays essential roles in embryonic development, especially in the development of lung mesenchymal cells. Its dysregulation is associated with various cancers, such as melanoma, prostate cancer, and breast cancer, as well as sevoflurane-induced cognitive disorder. Studies using mouse models, like genetic lineage tracing in the lung and functional studies in cancer cells, have been crucial in revealing these functions, providing insights into potential therapeutic targets for related diseases.