Huang Yumeng, Wang Pei, Morales Rodrigo, Luo Qi, Ma Jianfang
Department of Neurology, Institute of Neurology, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China.
Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States.
Front Aging Neurosci. 2021 Jun 8;13:651638. doi: 10.3389/fnagi.2021.651638. eCollection 2021.
MAP2K5, a member of the MAPK family, is associated with central nervous system disorders. However, neural functional of Map2k5 from animal models were not well examined so far. Here, we established a Map2k5-targeted knockout mouse model to investigate the behavior phenotypes and its underlying molecular mechanism. Our results showed that female Map2k5 mutant mice manifested decreased circadian-dependent ambulatory locomotion, coordination, and fatigue. Male Map2k5 mutant mice displayed impairment in open field exploration and prepulse inhibition of acoustic startle response (ASR) when compared with wild-type controls. Furthermore, Map2k5 mutant mice showed a decreased dopaminergic cell survival and tyrosine hydroxylase levels in nigrostriatal pathway, indicating a crucial role of MAP2K5 in regulating dopamine system in the central nervous system. In conclusion, this is the first study demonstrating that Map2k5 mutant mice displayed phenotypes by disturbing the dopamine system in the central nervous system, implicating Map2k5 mutant mouse as a promising model for many dopamine related disorders.
MAP2K5是丝裂原活化蛋白激酶（MAPK）家族的成员之一，与中枢神经系统疾病有关。然而，迄今为止，动物模型中Map2k5的神经功能尚未得到充分研究。在此，我们建立了一个靶向敲除Map2k5的小鼠模型，以研究其行为表型及其潜在的分子机制。我们的结果表明，雌性Map2k5突变小鼠表现出昼夜节律依赖性的自主运动、协调性和疲劳感下降。与野生型对照相比，雄性Map2k5突变小鼠在旷场探索和听觉惊吓反应（ASR）的前脉冲抑制方面表现出损伤。此外，Map2k5突变小鼠黑质纹状体通路中的多巴胺能细胞存活率和酪氨酸羟化酶水平降低，表明MAP2K5在调节中枢神经系统多巴胺系统中起关键作用。总之，这是第一项表明Map2k5突变小鼠通过干扰中枢神经系统中的多巴胺系统而表现出表型的研究，这意味着Map2k5突变小鼠是许多多巴胺相关疾病的一个有前景的模型。
