Mgat5 modulates the effect of early life stress on adult behavior and physical health in mice

• Mgat5−/− mice show a less depression-like phenotype.
• Mgat5−/− mice have higher bone density and lower blood glucose levels.
• Cortical neuron spine density is increased in Mgat5−/− males, decreased in females.

Psychosocial adversity in early life increases the likelihood of mental and physical illness, but the underlying mechanisms are poorly understood. Mgat5 is an N-acetylglucosaminyltransferase in the Golgi pathway that remodels the N-glycans of glycoproteins at the cell surface. Mice lacking Mgat5 display conditional phenotypes in behaviour, immunity, metabolism, aging and cancer susceptibility. Here we investigated potential gene-environment interactions between Mgat5 and early life adversity on behaviour and physiological measures of physical health. Mgat5−/− mutant and Mgat5+/+ wild-type C57Bl/6 littermates were subject to maternal separation or foster rearing as an early life stressor, in comparison to control mice reared normally. We found an interaction between Mgat5 genotype and maternal rearing condition in which Mgat5−/− mice subjected to early life stress had lower glucose levels and higher bone density. Mgat5−/− genotype was also associated with less immobility in the forced swim test and greater sucrose consumption, consistent with a less depression-like phenotype. Cortical neuron dendrite spine density and branching was altered by Mgat5 deletion as well. In general, Mgat5 genotype affects both behaviour and physical outcomes in response to early life stress, suggesting some shared pathways for both in this model. These results provide a starting point for studying the mechanisms by which protein N-glycosylation mediates the effects of early life adversity.