Morc1 knockout evokes a depression-like phenotype in mice.

Area of Science:

• Neuroscience
• Genetics
• Behavioral Science

Background:

• The Morc1 gene is implicated in major depressive disorder (MDD) associated with early life stress, identified through genetic and methylation studies.
• No established animal model currently exists to validate Morc1's role in MDD behaviorally.

Purpose of the Study:

• To investigate the behavioral effects of a Morc1 loss-of-function mutation in female mice.
• To assess if Morc1 deficiency leads to mood disorder-related behaviors and to explore underlying physiological changes.

Main Methods:

• Generation of Morc1 knockout (Morc1(-/-)) female mice on a C57BL/6N background.
• Behavioral testing using the Forced Swim Test, Learned Helplessness Paradigm, O-Maze, and Dark-Light-Box.
• Measurement of corticosterone (CORT) plasma levels and hippocampal Brain-Derived Neurotrophic Factor (Bdnf) mRNA levels.

Main Results:

• Morc1(-/-) mice displayed significantly increased depressive-like behavior compared to wildtype littermates.
• No significant differences were observed in locomotor activity or anxiety-like behaviors between the groups.
• While CORT levels were similar, hippocampal Bdnf mRNA levels were unexpectedly upregulated in Morc1(-/-) mice.

Conclusions:

• Morc1(-/-) mice exhibit a specific increase in depressive-like behaviors without altered anxiety or general activity.
• The findings suggest Morc1 plays a critical role in regulating mood, potentially through mechanisms involving hippocampal Bdnf.
• Morc1 knockout mice represent a promising, epigenetically validated model for studying depression linked to early life stress.