BAHD1 haploinsufficiency results in anxiety-like phenotypes in male mice

PLoS One. 2020 May 14;15(5):e0232789. doi: 10.1371/journal.pone.0232789. eCollection 2020.

Abstract

BAHD1 is a heterochomatinization factor recently described as a component of a multiprotein complex associated with histone deacetylases HDAC1/2. The physiological and patho-physiological functions of BAHD1 are not yet well characterized. Here, we examined the consequences of BAHD1 deficiency in the brains of male mice. While Bahd1 knockout mice had no detectable defects in brain anatomy, RNA sequencing profiling revealed about 2500 deregulated genes in Bahd1-/- brains compared to Bahd1+/+ brains. A majority of these genes were involved in nervous system development and function, behavior, metabolism and immunity. Exploration of the Allen Brain Atlas and Dropviz databases, assessing gene expression in the brain, revealed that expression of the Bahd1 gene was limited to a few territories and cell subtypes, particularly in the hippocampal formation, the isocortex and the olfactory regions. The effect of partial BAHD1 deficiency on behavior was then evaluated on Bahd1 heterozygous male mice, which have no lethal or metabolic phenotypes. Bahd1+/- mice showed anxiety-like behavior and reduced prepulse inhibition (PPI) of the startle response. Altogether, these results suggest that BAHD1 plays a role in chromatin-dependent gene regulation in a subset of brain cells and support recent evidence linking genetic alteration of BAHD1 to psychiatric disorders in a human patient.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / genetics*
  • Anxiety / physiopathology
  • Brain / metabolism*
  • Brain / pathology
  • Chromatin / genetics
  • Chromosomal Proteins, Non-Histone / genetics*
  • Gene Expression Regulation / genetics
  • Haploinsufficiency / genetics
  • Histone Deacetylase 1 / genetics
  • Histone Deacetylase 2 / genetics
  • Humans
  • Mice
  • Mice, Knockout
  • Phenotype
  • Reflex, Startle / genetics*
  • Sequence Analysis, RNA

Substances

  • BAHD1 protein, mouse
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Hdac1 protein, mouse
  • Hdac2 protein, mouse
  • Histone Deacetylase 1
  • Histone Deacetylase 2

Grants and funding

H.B. acknowledges support from Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (MICA grant) and the iXcore Foundation for Research. R.P received support from Ligue Nationale Contre le Cancer. Y.P acknowledges support from the French state funds through the “Agence Nationale de la Recherche” under the frame programme Investissements d’Avenir labelled ANR-10-IDEX-0002-02, ANR-10-LABX-0030-INRT, ANR-10-INBS-07 PHENOMIN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.