Transgenic mice carrying a tetracycline-inducible, truncated transforming growth factor beta receptor (TβRII)
Transgenic mice carrying a tetracycline-inducible, truncated transforming growth factor beta receptor (TβRII)
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DOI：
10.1002/gene.20115
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发表时间：
2005-05-01
期刊：
影响因子：
1.5
通讯作者：
McLennan, IS
中科院分区：
文献类型：
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作者：
Frugier, T;Koishi, K;McLennan, IS
转化生长因子 - β（TGF - β）具有多种作用，这使得对其功能的遗传学分析变得困难。因此，我们开发了转基因小鼠品系，利用一种可诱导、可逆且具有细胞类型特异性的机制来阻断TGF - β信号传导。转基因小鼠品系携带一种增强型绿色荧光蛋白 - pBi - ΔT - βRII构建体（PTR）。ΔTβRII元件编码一种显性负性受体，已知该受体可阻断TGF - β信号传导。ΔTβRII带有一个c - myc标签。在PTR小鼠中，转基因是沉默的，当PTR小鼠与表达四环素反式激活因子（CMV - tTA）的小鼠杂交时，增强型绿色荧光蛋白和ΔTβRII都会表达。通过在PTR×CMV - tTA小鼠的饮用水中添加多西环素，增强型绿色荧光蛋白的表达会受到抑制。然后将PTR小鼠与神经元特异性 - tTA小鼠杂交。在这些小鼠中，ΔTβRII转基因的表达导致天然TGF - β受体表达上调，这表明神经元能够调节其对TGF - β的反应性。（c）2005威利 - 利斯公司
The transforming growth factor-betas (TGF beta s) have multiple roles, making genetic analysis of their functions difficult. We therefore developed transgenic mouse lines to disrupt TGF beta signaling using a mechanism that is inducible, reversible, and cell-type specific. The transgenic mouse lines carry an EGFP-pBi-DeltaT-betaRII construct (PTR). The Delta T beta RII element codes for a dominant-negative receptor that is known to disrupt TGF beta signaling. The Delta T beta RII has a c-myc tag. The transgene was silent in the PTR mice, with expression of both EGFP and Delta T beta RII occurring when the PTR mice were crossed with mice that express the tetracycline transactivator (CMV-tTA). The expression of EGFP was repressed by the addition of doxycycline to the drinking water of the PTRxCMV-tTA mice. The PTR mice were then crossed with neuron-specific-tTA mice. Expression of the Delta T beta RII transgene in these mice led to an upregulation of native TGF beta receptor expression, suggesting that neurons can modulate their responsiveness to TGF beta s. (c) 2005 Wiley-Liss, Inc.