Telencephalon-specific Alkbh1 conditional knockout mice display hippocampal atrophy and impaired learning
| Autor: | Ryo Saito, Atsu Aiba, Masahiro Fukaya, Layla Kawarada, Hiroyuki Sakagami, Hidetoshi Kassai |
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| Rok vydání: | 2021 |
| Předmět: |
Biophysics
Hippocampus Morris water navigation task AlkB Homolog 1 Histone H2a Dioxygenase Hippocampal formation Biology Mitochondrion Biochemistry 03 medical and health sciences Gene Knockout Techniques Mice Structural Biology Conditional gene knockout Genetics medicine Animals Learning Molecular Biology CA1 Region Hippocampal 030304 developmental biology Mice Knockout 0303 health sciences Cerebrum Pyramidal Cells 030302 biochemistry & molecular biology Respiratory chain complex Cell Biology medicine.anatomical_structure nervous system Knockout mouse Atrophy Neuroscience |
| Zdroj: | FEBS lettersReferences. 595(12) |
| ISSN: | 1873-3468 |
| Popis: | AlkB homolog 1 (ALKBH1) is responsible for the biogenesis of 5-formylcytidine (f5 C) on mitochondrial tRNAMet 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. |
| Databáze: | OpenAIRE |
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