Ku Chia-Chen, Wuputra Kenly, Kato Kohsuke, Pan Jia-Bin, Li Chia-Pei, Tsai Ming-Ho, Noguchi Michiya, Nakamura Yukio, Liu Chung-Jung, Chan Te-Fu, Hou Ming-Feng, Wakana Shigeharu, Wu Yang-Chang, Lin Chang-Shen, Wu Deng-Chyang, Yokoyama Kazunari K
Graduate Institute of Medicine, Regenerative Medicine and Cell Therapy Research Center, School of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, 807, Koahsiung, Taiwan.
Stem Cell Res Ther. 2021 Jun 29;12(1):369. doi: 10.1186/s13287-021-02424-4.
The cerebellum is the sensitive region of the brain to developmental abnormalities related to the effects of oxidative stresses. Abnormal cerebellar lobe formation, found in Jun dimerization protein 2 (Jdp2)-knockout (KO) mice, is related to increased antioxidant formation and a reduction in apoptotic cell death in granule cell progenitors (GCPs). Here, we aim that Jdp2 plays a critical role of cerebellar development which is affected by the ROS regulation and redox control.
Jdp2-promoter-Cre transgenic mouse displayed a positive signal in the cerebellum, especially within granule cells. Jdp2-KO mice exhibited impaired development of the cerebellum compared with wild-type (WT) mice. The antioxidation controlled gene, such as cystine-glutamate transporter Slc7a11, might be critical to regulate the redox homeostasis and the development of the cerebellum.
We generated the Jdp2-promoter-Cre mice and Jdp2-KO mice to examine the levels of Slc7a11, ROS levels and the expressions of antioxidation related genes were examined in the mouse cerebellum using the immunohistochemistry.
The cerebellum of Jdp2-KO mice displayed expression of the cystine-glutamate transporter Slc7a11, within the internal granule layer at postnatal day 6; in contrast, the WT cerebellum mainly displayed Sla7a11 expression in the external granule layer. Moreover, development of the cerebellar lobes in Jdp2-KO mice was altered compared with WT mice. Expression of Slc7a11, Nrf2, and p21 was higher in the cerebellum of Jdp2-KO mice than in WT mice.
Jdp2 is a critical regulator of Slc7a11 transporter during the antioxidation response, which might control the growth, apoptosis, and differentiation of GCPs in the cerebellar lobes. These observations are consistent with our previous study in vitro.
小脑是大脑中对与氧化应激影响相关的发育异常敏感的区域。在Jun二聚化蛋白2（Jdp2）基因敲除（KO）小鼠中发现的异常小脑叶形成，与抗氧化剂生成增加和颗粒细胞祖细胞（GCP）凋亡细胞死亡减少有关。在此，我们旨在研究Jdp2在受活性氧（ROS）调节和氧化还原控制影响的小脑发育中起关键作用。
Jdp2启动子-Cre转基因小鼠在小脑中显示出阳性信号，尤其是在颗粒细胞内。与野生型（WT）小鼠相比，Jdp2-KO小鼠表现出小脑发育受损。抗氧化控制基因，如胱氨酸-谷氨酸转运体Slc7a11，可能对调节氧化还原稳态和小脑发育至关重要。
我们构建了Jdp2启动子-Cre小鼠和Jdp2-KO小鼠，以检测Slc7a11水平、ROS水平，并使用免疫组织化学方法检测小鼠小脑中抗氧化相关基因的表达。
Jdp2-KO小鼠的小脑在出生后第6天的内颗粒层显示出胱氨酸-谷氨酸转运体Slc7a11的表达；相比之下，野生型小脑主要在外颗粒层显示Sla7a11表达。此外，与野生型小鼠相比，Jdp2-KO小鼠小脑叶的发育发生了改变。Jdp2-KO小鼠小脑中Slc7a11、Nrf2和p21的表达高于野生型小鼠。
Jdp2是抗氧化反应过程中Slc7a11转运体的关键调节因子，可能控制小脑叶中GCP的生长、凋亡和分化。这些观察结果与我们之前的体外研究一致。
