Telencephalon-specific Alkbh1 conditional knockout mice display hippocampal atrophy and impaired learning

FEBS Letters

article

Layla Kawarada¹  Masahiro Fukaya³  Ryo Saito¹  Hidetoshi Kassai¹  Hiroyuki Sakagami³  Atsu Aiba¹ 

[1] Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo;Department of Biological Sciences, School of Science, The University of Tokyo;Department of Anatomy, Kitasato University School of Medicine

关键词: Alkbh1;    hippocampus;    knockout mice;    learning and memory;    mitochondria;   

DOI  :  10.1002/1873-3468.14098

来源: John Wiley & Sons Ltd.

【 摘 要 】

AlkB homolog 1 (ALKBH1) is responsible for the biogenesis of 5-formylcytidine (f 5 C) on mitochondrial tRNA Met and essential for mitochondrial protein synthesis. The brain, especially the hippocampus, is highly susceptible to mitochondrial dysfunction; hence, the maintenance of mitochondrial activity is strongly required to prevent disorders associated with hippocampal malfunction. To study the role of ALKBH1 in the hippocampus, we generated dorsal telencephalon-specific Alkbh1 conditional knockout (cKO) mice in inbred C57BL/6 background. These mice showed reduced activity of the respiratory chain complex, hippocampal atrophy, and CA1 pyramidal neuron abnormalities. Furthermore, performances in the fear-conditioning and Morris water maze tests in cKO mice indicated that the hippocampal abnormalities led to impaired hippocampus-dependent learning. These findings indicate critical roles of ALKBH1 in the hippocampus.

【 授权许可】

Unknown