# Gene expression differences in the olfactory bulb associated with differential social interactions and olfactory deficits in Pax6 heterozygous mice

## TL;DR

Pax6 heterozygous mice show social and olfactory issues due to imbalanced brain activity and gene regulation changes.

## Contribution

Identifies gene expression changes in the olfactory bulb linked to social and olfactory deficits in Pax6 heterozygous mice.

## Key findings

- Aberrant social interactions and olfactory deficits are observed in Pax6 heterozygous mice.
- Transcriptome analysis reveals imbalances in neuronal excitation and inhibition, synaptic dysfunction, and epigenetic changes.
- Findings overlap with autism-associated genes, suggesting a link to autistic-like behaviors.

## Abstract

Mutations in the highly conserved Pax6 transcription factor have been implicated in neurodevelopmental disorders and behavioral abnormalities, yet the mechanistic basis of the latter remain poorly understood. Our study, using behavioral phenotyping, has identified aberrant social interactions, characterized by withdrawal behavior, and olfactory deficits in Pax6 heterozygous mutant mice. The molecular mechanisms underlying the observed phenotypes were characterized by means of RNA-sequencing on isolated olfactory bulbs followed by validation with qRT-PCR. Comparative analysis of olfactory bulb transcriptomes further reveals an imbalance between neuronal excitation and inhibition, synaptic dysfunction, and alterations in epigenetic regulation as possible mechanisms underlying the abnormal social behavior. We observe a considerable overlap with autism-associated genes and suggest that studying Pax6-dependent gene regulatory networks may further our insight into molecular mechanisms implicated in autistic-like behaviors in Pax6 mutations, thereby paving the way for future research in this area.

Summary: Pax6 heterozygous mutant mice display aberrant social interactions and olfactory deficits caused by an imbalance between neuronal excitation and inhibition, synaptic dysfunction, and alterations in epigenetic regulation.