Duplicated dnmt3aa and dnmt3ab DNA Methyltransferase Genes Play Essential and Non-Overlapped Functions on Modulating Behavioral Control in Zebrafish

Genes

OliverB. Villaflores¹  MichaelEdbert Suryanto²  Sung-Tzu Liang²  Yu-Heng Lai³  Gilbert Audira⁴  Chung-Der Hsiao⁴  Petrus Siregar⁴  Omar Villalobos⁵  Huan-Chau Lin⁶  Ken-Hong Lim⁶  Erwei Hao⁷ 

[1] Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Manila 1015, Philippines;Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li 320314, Taiwan;Department of Chemistry, Chinese Culture University, Taipei 11114, Taiwan;Department of Chemistry, Chung Yuan Christian University, Chung-Li 320314, Taiwan;Department of Pharmacy, Faculty of Pharmacy, University of Santo Tomas, Manila 1015, Philippines;Division of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Number 92, Section 2, Chungshan North Road, Taipei 10449, Taiwan;Guangxi Scientific Experimental Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning 530200, Guangxi, China;

关键词: Danio rerio;    anxiety;    behavior;    DNA methylation profiling;    epigenetic;   

DOI  :  10.3390/genes11111322

来源: DOAJ

【 摘 要 】

DNA methylation plays several roles in regulating neuronal proliferation, differentiation, and physiological functions. The major de novo methyltransferase, DNMT3, controls the DNA methylation pattern in neurons according to environmental stimulations and behavioral regulations. Previous studies demonstrated that knockout of Dnmt3 induced mouse anxiety; however, controversial results showed that activation of Dnmt3 causes anxiolytic behavior. Thus, an alternative animal model to clarify Dnmt3 on modulating behavior is crucial. Therefore, we aimed to establish a zebrafish (Danio rerio) model to clarify the function of dnmt3 on fish behavior by behavioral endpoint analyses. We evaluated the behaviors of the wild type, dnmt3aa, and dnmt3ab knockout (KO) fish by the novel tank, mirror biting, predator avoidance, social interaction, shoaling, circadian rhythm locomotor activity, color preference, and short-term memory tests. The results indicated that the dnmt3aa KO fish possessed abnormal exploratory behaviors and less fear response to the predator. On the other hand, dnmt3ab KO fish displayed less aggression, fear response to the predator, and interests to interact with their conspecifics, loosen shoaling formation, and dysregulated color preference index ranking. Furthermore, both knockout fishes showed higher locomotion activity during the night cycle, which is a sign of anxiety. However, changes in some neurotransmitter levels were observed in the mutant fishes. Lastly, whole-genome DNA methylation sequencing demonstrates a potential network of Dnmt3a proteins that is responsive to behavioral alterations. To sum up, the results suggested that the dnmt3aa KO or dnmt3ab KO fish display anxiety symptoms, which supported the idea that Dnmt3 modulates the function involved in emotional control, social interaction, and cognition.

【 授权许可】

Unknown