title: Cognition and mood-related behaviors in L3mbtl1 null mutant mice.
abstract: Alterations in histone lysine methylation and epigenetic regulators of gene expression could play a role in the neurobiology and treatment of patients diagnosed with mood spectrum disorder, including depression and anxiety. Mutations and altered expression of various lysine methyltransferases (KMTs) and demethylases (KDMs) have been linked to changes in motivational and emotional behaviors in preclinical model systems. However, it is not known whether regulators operating downstream of histone lysine methylation could affect mood-related behavior. Malignant Brain Tumor (MBT) domain 'chromatin reader' proteins bind to methylated histone lysine residues and associate with chromatin remodeling complexes to facilitate or repress gene expression. MBT proteins, including the founding member, L3mbtl1, maintain high levels of expression in neurons of the mature brain. Here, we exposed L3mbtl1 null mutant mice to a wide range of tests exploring cognition and mood-relevant behaviors at baseline and in the context of social isolation, as a stressor to elicit depression-related behavior in susceptible mice. L3mbtl1 loss-of-function was associated with significant decreases in depression and and anxiety in some of the behavioral paradigms. This was not associated with a more generalized neurological dysfunction because cognition and memory remained unaltered in comparison to controls. These findings warrant further investigations on the role of MBT chromatin reader proteins in the context of emotional and affective behaviors.
authors: Department of Psychiatry, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, United States of America.
authors: Erica Y
authors: EY
authors: Shen
authors: Department of Psychiatry, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, United States of America.
authors: Yan
authors: Y
authors: Jiang
authors: Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, Massachusetts, 01604, United States of America.
authors: Wenjie
authors: W
authors: Mao
authors: Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, Massachusetts, 01604, United States of America.
authors: Kensuke
authors: K
authors: Futai
authors: Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, 02114, United States of America.
authors: Hanno
authors: H
authors: Hock
authors: Department of Psychiatry, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, United States of America.
authors: Schahram
authors: S
authors: Akbarian
mesh_terms: D000339:Affect; D000818:Animals; D001522:Behavior, Animal; D003071:Cognition; D003863:Depression / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008568:Memory; D051379:Mice; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000172:deficiency*; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins / Q000172:deficiency*
chemical_list: C552439:L3MBTL1 protein, mouse; D009687:Nuclear Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins