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Open AccessArticle

Zebrafish Mutants Carrying Leptin a (lepa) Gene Deficiency Display Obesity, Anxiety, Less Aggression and Fear, and Circadian Rhythm and Color Preference Dysregulation

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Department of Chemistry, Chung Yuan Christian University, Chung-Li 32023, Taiwan
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Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan
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Department of Biological Science & Technology College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan
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Department of Chemistry, Chinese Culture University, Taipei 11114, Taiwan
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Laboratory of Marine Biology and Ecology, Third Institute of Oceanography, State OceanicAdministration, Xiamen 361005, China
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Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua 50094, Taiwan
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Center of Nanotechnology, Chung Yuan Christian University, Chung-Li 32023, Taiwan
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Center of Biomedical Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan
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Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(12), 4038; https://doi.org/10.3390/ijms19124038
Received: 9 November 2018 / Revised: 5 December 2018 / Accepted: 11 December 2018 / Published: 13 December 2018
Leptin, a hormone secreted by peripheral adipose tissues, regulates the appetite in animals. Recently, evidence has shown that leptin also plays roles in behavioral response in addition to controlling appetite. In this study, we examined the potential function of leptin on non-appetite behaviors in zebrafish model. By using genome editing tool of Transcription activator-like effector nuclease (TALEN), we successfully knocked out leptin a (lepa) gene by deleting 4 bp within coding region to create a premature-translation stop. Morphological and appetite analysis showed the lepa KO fish display a phenotype with obese, good appetite and elevation of Agouti-related peptide (AgRP) and Ghrelin hormones, consistent with the canonical function of leptin in controlling food intake. By multiple behavior endpoint analyses, including novel tank, mirror biting, predator avoidance, social interaction, shoaling, circadian rhythm, and color preference assay, we found the lepa KO fish display an anxiogenic phenotype showing hyperactivity with rapid swimming, less freezing time, less fear to predator, loose shoaling area forming, and circadian rhythm and color preference dysregulations. Using biochemical assays, melatonin, norepinephrine, acetylcholine and serotonin levels in the brain were found to be significantly reduced in lepa KO fish, while the levels of dopamine, glycine and cortisol in the brain were significantly elevated. In addition, the brain ROS level was elevated, and the anti-oxidative enzyme catalase level was reduced. Taken together, by performing loss-of-function multiple behavior endpoint testing and biochemical analysis, we provide strong evidence for a critical role of lepa gene in modulating anxiety, aggression, fear, and circadian rhythm behaviors in zebrafish for the first time. View Full-Text
Keywords: leptin; obesity; zebrafish; behavior; anxiety; aggression; fear; circadian rhythm; color preference; genome editing; TALEN leptin; obesity; zebrafish; behavior; anxiety; aggression; fear; circadian rhythm; color preference; genome editing; TALEN
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Audira, G.; Sarasamma, S.; Chen, J.-R.; Juniardi, S.; Sampurna, B.P.; Liang, S.-T.; Lai, Y.-H.; Lin, G.-M.; Hsieh, M.-C.; Hsiao, C.-D. Zebrafish Mutants Carrying Leptin a (lepa) Gene Deficiency Display Obesity, Anxiety, Less Aggression and Fear, and Circadian Rhythm and Color Preference Dysregulation. Int. J. Mol. Sci. 2018, 19, 4038.

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