Wang Min, Liu Xiaojuan, Fang Yin, Li Qintong
Departments of Laboratory Medicine, Obstetrics & Gynecology and Pediatrics, West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu, Sichuan, China.
Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Front Cell Dev Biol. 2024 Oct 16;12:1480217. doi: 10.3389/fcell.2024.1480217. eCollection 2024.
Individuals with neurodevelopmental disorders (NDDs) are frequently diagnosed with comorbidities in other organs, indicating that NDD risk genes may have extra-cerebral functions. The engineered mouse models are pivotal in understanding the functions of candidate NDD genes. Here, we report that Emx1-Cre and nestin-Cre mouse strains, the popular tools to study brain development, also exhibit recombination activity in the kidney. We find that both Emx1-Cre and nestin-Cre can drive recombination in epithelial cells lining proximal and distal convoluted tubules of the nephron. Additionally, nestin-Cre drives recombination in the glomerulus of the nephron. Furthermore, we use Emx1-Cre and nestin-Cre to knock out , a gene linked to a human NDD called Alazami syndrome. We find that knockout using nestin-Cre, but not Emx1-Cre, results in elevated blood urea nitrogen. This result suggests a compromised kidney function, reminiscent of recently revealed renal anomalies in Alazami syndrome patients. Many genes have been knocked out using Emx1-Cre and nestin-Cre to study their roles during embryonic neurogenesis. It will be of great interest to reinvestigate whether the renal development and function is affected in these existing mouse models.
患有神经发育障碍（NDDs）的个体常常被诊断出合并有其他器官的疾病，这表明NDD风险基因可能具有脑外功能。工程小鼠模型对于理解候选NDD基因的功能至关重要。在此，我们报告称，Emx1-Cre和巢蛋白-Cre小鼠品系这两种研究大脑发育的常用工具，在肾脏中也表现出重组活性。我们发现Emx1-Cre和巢蛋白-Cre都能驱动肾单位近端和远端曲管内衬上皮细胞的重组。此外，巢蛋白-Cre能驱动肾单位肾小球的重组。再者，我们使用Emx1-Cre和巢蛋白-Cre敲除了一个与名为阿拉扎米综合征的人类NDD相关的基因。我们发现，使用巢蛋白-Cre而非Emx1-Cre敲除该基因会导致血尿素氮升高。这一结果提示肾功能受损，这让人联想到最近在阿拉扎米综合征患者中发现的肾脏异常。许多基因已通过Emx1-Cre和巢蛋白-Cre敲除来研究它们在胚胎神经发生过程中的作用。重新研究这些现有的小鼠模型中肾脏发育和功能是否受到影响将非常有趣。
