Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Developmental Disability Center, 713-8 Kamiya, Kasugai 480-0392, Japan.
Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Cells. 2024 Mar 19;13(6):540. doi: 10.3390/cells13060540.
POGZ (Pogo transposable element derived with ZNF domain) is known to function as a regulator of gene expression. While variations in the gene have been associated with intellectual disabilities and developmental delays in humans, the exact pathophysiological mechanisms remain unclear. To shed light on this, we created two lines of conditional knockout mice for , one specific to excitatory neurons (Emx1-Pogz mice) and the other to inhibitory neurons (Gad2-Pogz mice) in the brain. Emx1-Pogz mice showed a decrease in body weight, similar to total knockout mice. Although the two lines did not display significant morphological abnormalities in the telencephalon, impaired POGZ function affected the electrophysiological properties of both excitatory and inhibitory neurons differently. These findings suggest that these mouse lines could be useful tools for clarifying the precise pathophysiological mechanisms of neurodevelopmental disorders associated with gene abnormalities.
POGZ（具有 ZNF 结构域的 Pogo 转座元件）已知作为基因表达的调节剂发挥作用。虽然该基因的变异与人类的智力残疾和发育迟缓有关，但确切的病理生理机制仍不清楚。为了阐明这一点，我们在大脑中创建了两条针对 的条件性敲除小鼠品系，一条针对兴奋性神经元（Emx1-Pogz 小鼠），另一条针对抑制性神经元（Gad2-Pogz 小鼠）。Emx1-Pogz 小鼠的体重下降，与总 敲除小鼠相似。尽管这两种品系在端脑中没有表现出明显的形态异常，但 POGZ 功能的受损对兴奋性和抑制性神经元的电生理特性有不同的影响。这些发现表明，这些小鼠品系可能是阐明与 基因异常相关的神经发育障碍的确切病理生理机制的有用工具。
