Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), College of Fisheries, Research Center of Fishery Resources and Environment, Southwest University, Chongqing 400715, China.
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
Int J Mol Sci. 2023 Feb 14;24(4):3849. doi: 10.3390/ijms24043849.
Protein kinase Cα (PKCα/PRKCA) is a crucial regulator of circadian rhythm and is associated with human mental illnesses such as autism spectrum disorders and schizophrenia. However, the roles of PRKCA in modulating animal social behavior and the underlying mechanisms remain to be explored. Here we report the generation and characterization of -deficient zebrafish (). The results of behavioral tests indicate that a deficiency in Prkcaa led to anxiety-like behavior and impaired social preference in zebrafish. RNA-sequencing analyses revealed the significant effects of the mutation on the expression of the morning-preferring circadian genes. The representatives are the immediate early genes, including , , , and . The downregulation of these genes at night was attenuated by Prkcaa dysfunction. Consistently, the mutants demonstrated reversed day-night locomotor rhythm, which are more active at night than in the morning. Our data show the roles of PRKCA in regulating animal social interactions and link the social behavior defects with a disturbed circadian rhythm.
蛋白激酶 Cα（PKCα/PRKCA）是生物钟的关键调节因子，与自闭症谱系障碍和精神分裂症等人类精神疾病有关。然而，PRKCA 在调节动物社交行为中的作用及其潜在机制仍有待探索。在这里，我们报告了 PRKCAa 基因敲除斑马鱼（）的产生和特征。行为测试的结果表明，Prkcaa 的缺失导致斑马鱼表现出类似焦虑的行为和受损的社交偏好。RNA-seq 分析显示，突变对晨型生物钟基因的表达有显著影响。其代表是即时早期基因，包括 、 、 、 和 。这些基因在夜间的下调被 Prkcaa 功能障碍减弱。一致地，突变体表现出昼夜运动节律的反转，它们在夜间比在早晨更活跃。我们的数据显示了 PRKCA 在调节动物社交互动中的作用，并将社交行为缺陷与紊乱的生物钟联系起来。
