Mice with a targeted intronic deletion in the Col1a1 gene respond to bleomycin-induced pulmonary fibrosis with increased expression of the mutant allele.
Mice with a targeted intronic deletion in the Col1a1 gene respond to bleomycin-induced pulmonary fibrosis with increased expression of the mutant allele.
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Col1a1 基因中有针对性的内含子缺失的小鼠对博来霉素诱导的肺纤维化有反应，突变等位基因的表达增加。
DOI：
10.1016/s0945-053x(99)00017-7
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Bornstein,P
中科院分区：
文献类型：
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作者：
Hormuzdi,SG;Strandjord,TP;Madtes,DK;Bornstein,P
旨在检查第一个内含子在通过转染和转基因小鼠调节 Col1a1 基因中的作用的实验得出了相互矛盾的结论。最近，霍尔木兹迪等人。 [Hormuzdi, S.G.、Penttinen, R.、Jaenisch, R.、Bornstein, P., 1998。基因靶向方法确定了第一个内含子在 α1(I) 胶原蛋白表达中的功能。摩尔。细胞。生物。 18, 3368–3375.] 在小鼠的这个内含子中创建了一个有针对性的删除，并证明了肺和骨骼肌中突变等位基因表达的年龄依赖性减少。在这项研究中，通过向小鼠气管内滴注博莱霉素来诱导对照和内含子缺失动物的肺纤维化。这种对胶原蛋白合成的刺激与突变小鼠中内含子缺失等位基因的显着上调有关。我们的结果表明，突变型 Col1a1 基因的表达抑制不是固定的，因为该基因仍然可以对生理信号做出反应。我们提出，基因中其他位置的顺式作用元件可以补偿突变的 Col1a1 等位基因中内含子序列的缺失，并解释抑制的条件性质。该模型有可能解决先前使用 Col1a1 基因不同片段的转染和转基因实验的相互矛盾的结果。
Experiments designed to examine the role of the first intron in regulation of the Col1a1 gene by transfection and in transgenic mice have led to conflicting conclusions. Recently, Hormuzdi et al. [Hormuzdi, S.G., Penttinen, R., Jaenisch, R., Bornstein, P., 1998. A gene-targeting approach identifies a function for the first intron in expression of the α1(I) collagen. Mol. Cell. Biol. 18, 3368–3375.] created a targeted deletion in this intron in mice and demonstrated an age-dependent reduction in expression of the mutated allele in lung and skeletal muscle. In this study, intratracheal instillation of bleomycin in mice was used to induce pulmonary fibrosis in control and intron-deleted animals. This stimulus for collagen synthesis was associated with a marked upregulation of the intron-deleted allele in mutant mice. Our results establish that the inhibition of expression of the mutant Col1a1 gene is not fixed, since the gene can still respond to physiological signals. We propose that cis-acting elements, elsewhere in the gene, can compensate for the lack of intronic sequences in the mutated Col1a1 allele and account for the conditional nature of the inhibition. This model has the potential to resolve the conflicting results of previous transfection and transgenic experiments in which different fragments of the Col1a1 gene were used.