Beta N-acetylglucosaminyltransferase V (Mgat5) deficiency reduces the depression-like phenotype in mice

L. Soleimani, J. C. Roder, J. W. Dennis, T. Lipina

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


The central nervous system (CNS) is rich in glycoconjugates, located on cell surface and in extracellular matrix. The products of Golgi UDP-GlcNAc:N-acetylglucosaminyltransferases (encoded by Mgat1, Mgat2, Mgat4 and Mgat5) act sequentially to generate the GlcNAc-branched complex-type N-glycans on glycoprotein receptors. While elimination of all the branched N-glycans in Mgat1-/- mouse embryos is lethal at neural tube fold stage, decreased branching is associated with late developmental defects similar to type 2 of congenital disorders of glycosylation, with developmental and psychomotor abnormalities. To study the role of complex-type N-glycans in brain function, we tested Mgat5-/- mice in a battery of neurological and behavioral tests. Despite the absence of tri- and tetra-antennary products, Mgat5 -/- mice were not different from their wild-type littermates in physical and neurological assessments, anxiety level, startle reactivity and sensorimotor gating. However, they displayed a robust decrease in the immobility time in the forced swim test and the tail suspension test independent of locomotor activity, interpreted as a change in depression-like behavior. This effect was accentuated after chronic mild stress. Comparable increase in plasma corticosterone of Mgat5+/+ and Mgat5-/- mice in response to acute stress shows an intact function of the hypothalamus-pituitary-adrenal axis. A change in social interactions was also observed. Our results indicate that Mgat5 modification of complex-type N-glycans on CNS glycoproteins is involved in the regulation of depression-like behavior.

Original languageEnglish
Pages (from-to)334-343
Number of pages10
JournalGenes, Brain and Behavior
Issue number3
StatePublished - Apr 2008
Externally publishedYes


  • Animal models
  • Complex-type N-glycans
  • Depression-like behavior
  • Mgat5 knockout mice
  • Stress


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