Generation and characterization of Atoh1-Cre knock-in mouse line.
Generation and characterization of Atoh1-Cre knock-in mouse line.
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作者：
Yang, Hua;Xie, Xiaoling;Deng, Min;Chen, Xiaowei;Gan, Lin
Atoh 1编码一种碱性螺旋-环-螺旋（bHLH）转录因子，该因子是内耳感觉上皮、脊髓背侧、脑干、小脑和肠分泌细胞发育所必需的。在这项研究中，我们创建了一个遗传工具，研究在耳感觉器官的基因功能，我们产生了Atoh 1-Cre敲入小鼠系，通过替换整个Atoh 1编码序列与Cre编码序列。Atoh 1Cre/+小鼠存活，可生育，没有明显缺陷，而Atoh 1Cre/Cremice在围产期死亡。通过将Atoh 1-Cre小鼠与R26 R-lacZ条件报告小鼠杂交来检查Cre重组酶的时空活性。Atoh 1-Cre活性在发育中的内耳、后脑、脊髓和肠中检测到。在内耳中，Atoh 1-Cre活动仅限于感觉器官，其中lacZ表达在几乎所有的毛细胞和许多支持细胞中被检测到。因此，Atoh 1-Cre小鼠系可作为内耳基因功能研究的有用工具。此外，我们的研究结果表明，Atoh 1是在共同的祖细胞注定为头发和支持细胞的表达。
Atoh1 encodes a basic helix-loop-helix (bHLH) transcription factor required for the development of the inner ear sensory epithelia, the dorsal spinal cord, brainstem, cerebellum, and intestinal secretory cells. In this study to create a genetic tool for the research on gene function in the ear sensory organs, we generated an Atoh1-Cre knock-in mouse line by replacing the entire Atoh1 coding sequences with the Cre coding sequences. Atoh1Cre/+mice were viable, fertile, and displayed no visible defects whereas the Atoh1Cre/Cremice died perinatally. The spatiotemporal activities of Cre recombinase were examined by crossing Atoh1-Cre mice with the R26R-lacZ conditional reporter mice. Atoh1-Cre activities were detected in the developing inner ear, the hindbrain, the spinal cord, and the intestine. In the inner ear, Atoh1-Cre activities were confined to the sensory organs in which lacZ expression is detected in nearly all of the hair cells and in many supporting cells. Thus, Atoh1-Cre mouse line serves as a useful tool for the functional study of genes in the inner ear. In addition, our results demonstrate that Atoh1 is expressed in the common progenitors destined for both hair and supporting cells.
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