BAHD1 haploinsufficiency results in anxiety-like phenotypes in male mice

Renaud Pourpre (1) , Laurent Naudon (1) , Hamid Meziane (2) , Goran Lakisic (1) , Luc Jouneau (3) , Hugo Varet (4, 5) , Rachel Legendre (4, 5) , Olivia Wendling (2) , Mohammed Selloum (2) , Caroline Proux (5) , Jean-Yves Coppée (5) , Yann Hérault (2, 6) , Hélène Bierne (1)

1 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé
2 ICS - Institut Clinique de la Souris
3 VIM (UR 0892) - Virologie et Immunologie Moléculaires
4 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
5 C2RT - Pôle Biomics
6 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire

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.

Keywords: male mice; haploinsufficiency; phenotypes

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Neurons and Cognition [q-bio.NC]; Neurobiology; Life Sciences [q-bio]; Genetics

Renaud Pourpre, Laurent Naudon, Hamid Meziane, Goran Lakisic, Luc Jouneau, et al.. BAHD1 haploinsufficiency results in anxiety-like phenotypes in male mice. PLoS ONE, 2020, 15 (5), pp.e0232789. ⟨10.1371/journal.pone.0232789⟩. ⟨pasteur-02585985⟩