Generation of mice with a conditional allele for transforming growth factor beta 1 gene.
Generation of mice with a conditional allele for transforming growth factor beta 1 gene.
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DOI：
10.1002/dvg.20516
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发表时间：
2009-06
期刊：
影响因子：
1.5
通讯作者：
Doetschman, Thomas
中科院分区：
文献类型：
--
作者：
Azhar, Mohamad;Yin, Moying;Bommireddy, Ramireddy;Duffy, John J.;Yang, Junqi;Pawlowski, Sharon A.;Boivin, Gregory P.;Engle, Sandra J.;Sanford, L. P.;Grisham, Christina;Singh, Ram R.;Babcock, George F.;Doetschman, Thomas
转化生长因子β1（TGFβ1）是一种多功能生长因子，参与伤口愈合、组织纤维化和许多综合征性疾病（例如，马凡氏综合征、Camurati-Engelmann病）和肌肉、神经、眼科、心血管和免疫疾病以及癌症。自从Tgfb 1基因敲除小鼠产生以来，在了解其生理和病理生理功能方面取得了非凡的进展。在这里，我们报告了一个条件性敲除等位基因Tgfb 1，其中其外显子6两侧的LoxP位点的一代。作为原理的证明，我们将这些小鼠与LckCre转基因小鼠杂交，并特异性破坏T细胞中的Tgfb 1。结果表明，T细胞产生的TGFβ1是外周T细胞活化、维持T细胞稳态和抑制自身免疫的正常体内调节所必需的。
Transforming growth factor β1 (TGFβ1) is a multifunctional growth factor involved in wound healing, tissue fibrosis, and in the pathogenesis of many syndromic diseases (e.g., Marfan syndrome, Camurati-Engelmann disease) and muscular, neurological, ophthalmic, cardiovascular and immunological disorders, and cancer. Since the generation of Tgfb1 knockout mice, there has been extraordinary progress in understanding its physiological and pathophysiological function. Here, we report the generation of a conditional knockout allele for Tgfb1 in which its exon 6 is flanked with LoxP sites. As proof of principle, we crossed these mice to LckCre transgenic mice and specifically disrupted Tgfb1 in T cells. The results indicate that T-cell-produced TGFβ1 is required for normal in vivo regulation of peripheral T-cell activation, maintenance of T-cell homeostasis, and suppression of autoimmunity.
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