Dong Xuhui, Xie Xiaoling, Guo Luming, Xu Jiadong, Xu Mei, Liang Guoqing, Gan Lin
College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
Department of Ophthalmology and Flaum Eye Institute, University of Rochester, Rochester, New York.
Genesis. 2019 Oct;57(10):e23328. doi: 10.1002/dvg.23328. Epub 2019 Jul 17.
LHX4 is a LIM-homeodomain transcription factor essential for the development of spinal cord and pituitary gland. Mice with homozygous Lhx4-null mutation suffer early postnatal death from lung defect. In this study, to facilitate the research on Lhx4 function, we designed a targeting construct to generate two novel Lhx4 mouse lines: Lhx4 conditional knockout and Lhx4 reporter knock-in mice. Lhx4 , Lhx4 , and Lhx4 were viable, fertile, and did not display any gross abnormalities. By breeding Lhx4 line with Cre-expressing mice, the Exon 3 of Lhx4 was efficiently removed, resulting in a shift in the reading frame and the inactivation of Lhx4. The expression of tdTomato knock-in reporter recapitulated the endogenous LHX4 expression and was detected in the retina, spinal cord, pituitary gland, and hindbrain of Lhx4 mice. Thus, Lhx4 and Lhx4 mouse lines provide valuable tools for unraveling the tissue-specific role of Lhx4 at postnatal stages in mice.
LHX4是一种LIM同源结构域转录因子,对脊髓和垂体的发育至关重要。纯合Lhx4基因敲除突变的小鼠在出生后早期因肺部缺陷而死亡。在本研究中,为便于对Lhx4功能进行研究,我们设计了一种打靶载体,以产生两种新型的Lhx4小鼠品系:Lhx4条件性敲除小鼠和Lhx4报告基因敲入小鼠。Lhx4 +/-, Lhx4 +/fl, 和Lhx4 tm1.1(cre)Jax小鼠均存活、可育,且未表现出任何明显异常。通过将Lhx4 +/fl品系与表达Cre的小鼠杂交,Lhx4的外显子3被有效去除,导致阅读框移位和Lhx4失活。敲入报告基因tdTomato的表达重现了内源性LHX4的表达,并在Lhx4 tm1.1(cre)Jax小鼠的视网膜、脊髓、垂体和后脑检测到。因此,Lhx4 +/fl和Lhx4 tm1.1(cre)Jax小鼠品系为揭示出生后阶段Lhx4在小鼠体内的组织特异性作用提供了有价值的工具。