Morc1 knockout evokes a depression-like phenotype in mice.
Morc1 gene has recently been identified by a DNA methylation and genome-wide association study as a candidate gene for major depressive disorder related to early life stress in rodents, primates and humans. So far, no transgenic animal model has been established to validate these findings on a behavioral level. In the present study, we examined the effects of a Morc1 loss of function mutation in female C57BL/6N mice on behavioral correlates of mood disorders like the Forced Swim Test, the Learned Helplessness Paradigm, O-Maze and Dark-Light-Box. We could show that Morc1(-/-) mice display increased depressive-like behavior whereas no behavioral abnormalities regarding locomotor activity or anxiety-like behavior were detectable. CORT plasma levels did not differ significantly between Morc1(-/-) mice and their wildtype littermates, yet - surprisingly - total Bdnf mRNA-levels in the hippocampus were up-regulated in Morc1(-/-) animals. Although further work would be clarifying, Morc1(-/-) mice seem to be a promising epigenetically validated mouse model for depression associated with early life stress.
Central Institute of Mental Health Mannheim (ZI), Medical Faculty of Mannheim, University of Heidelberg, J5, D-68159, Mannheim, Germany. Electronic address: michaela.schmidt@zi-mannheim.de.
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Schmidt
Central Institute of Mental Health Mannheim (ZI), Medical Faculty of Mannheim, University of Heidelberg, J5, D-68159, Mannheim, Germany.
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Brandwein
Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti, 9, I-20133, Milan, Italy.
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Luoni
Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti, 9, I-20133, Milan, Italy.
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Sandrini
Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti, 9, I-20133, Milan, Italy.
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Calzoni
Central Institute of Mental Health Mannheim (ZI), Medical Faculty of Mannheim, University of Heidelberg, J5, D-68159, Mannheim, Germany.
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Deuschle
Behavioural Neuroscience Section, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161, Rome, Italy.
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Cirulli
Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti, 9, I-20133, Milan, Italy.
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Riva
Central Institute of Mental Health Mannheim (ZI), Medical Faculty of Mannheim, University of Heidelberg, J5, D-68159, Mannheim, Germany.
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Gass
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003863:Depression / Q000235:genetics*; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
D019208:Brain-Derived Neurotrophic Factor; C120546:Morc1 protein, mouse; D009687:Nuclear Proteins; D012333:RNA, Messenger
Bdnf; Depression; Early life stress; Epigenetics; Morc1; Transgenic mice