Kofuji Satoshi, Qian Yiming, Nishina Hiroshi
Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Sci Rep. 2025 Jul 1;15(1):20504. doi: 10.1038/s41598-025-05388-0.
The stress-responsive kinase MKK7 controls various brain functions. Previously, we showed that neural stem cell-specific deletion of the Mkk7 gene caused abnormal brain development and death immediately after birth (perinatal lethality). However, the region-specific roles of MKK7 during embryonic brain development remain unclear. In this study, we generated three strains of conditional Mkk7 knockout (Mkk7 cKO) mice with deletion of Mkk7 specifically in either the spinal cord, or midbrain/cerebellum, or cerebrum. Loss of MKK7 in the the spinal cord had no effect on mouse embryonic viability, but mice lacking MKK7 in the midbrain/cerebellum displayed perinatal lethality. In contrast, mice with loss of MKK7 in the cerebrum were born at the expected Mendelian ratio but died within five weeks of birth. The brains of these latter mutants showed a thinner cerebral cortex, enlarged ventricles, and decreased phosphorylation of microtubule-associated protein 1B (MAP1B) compared to wild type (WT) brains. This work expands our knowledge of MKK7 functions in the brain and shows that this kinase regulates brain development and maturation in a region-specific manner.
应激反应激酶MKK7控制着多种脑功能。此前，我们发现神经干细胞特异性缺失Mkk7基因会导致出生后立即出现脑发育异常和死亡（围产期致死）。然而，MKK7在胚胎脑发育过程中的区域特异性作用仍不清楚。在本研究中，我们构建了三株条件性Mkk7基因敲除（Mkk7 cKO）小鼠，分别在脊髓、中脑/小脑或大脑中特异性缺失Mkk7。脊髓中MKK7的缺失对小鼠胚胎活力没有影响，但中脑/小脑中缺乏MKK7的小鼠表现出围产期致死。相比之下，大脑中MKK7缺失的小鼠按预期孟德尔比例出生，但在出生后五周内死亡。与野生型（WT）小鼠的大脑相比，这些后一种突变体的大脑显示出大脑皮层变薄、脑室扩大以及微管相关蛋白1B（MAP1B）磷酸化水平降低。这项工作扩展了我们对MKK7在脑中功能的认识，并表明该激酶以区域特异性方式调节脑发育和成熟。
