Altered odor perception in Dlgap2 mutant mice, a mouse model of autism spectrum disorder

Yu-Fu Chen; Chih-Yu Tsao; Yuh-Tarng Chen; Ho-Ching Chang; Wai-Yu Li; Jui-Lin Chiang; Chien-Fu Fred Chen; Chia-Hsiang Chen; Susan Shur-Fen Gau; Kuang-Yung Lee; Li-Jen Lee; Yu-Chun Wang

doi:10.1016/j.bbr.2024.115365

Altered odor perception in Dlgap2 mutant mice, a mouse model of autism spectrum disorder

Behav Brain Res. 2024 Dec 2:480:115365. doi: 10.1016/j.bbr.2024.115365. Online ahead of print.

Authors

Affiliations

¹ Department of Neurology, Chang Gung Memorial Hospital, Keelung Branch, Keelung, Taiwan.
² Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
³ Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan.
⁴ Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
⁵ Department of Psychiatry, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan.
⁶ Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, Taiwan.
⁷ Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan; Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan; Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, Taiwan.
⁸ Department of Otolaryngology, Head and Neck Surgery, Chi-Mei Medical Center, Tainan, Taiwan. Electronic address: b94203061@gmail.com.

PMID: 39631506
DOI: 10.1016/j.bbr.2024.115365

Abstract

Olfactory dysfunction has been observed in patients with Autism Spectrum Disorder (ASD). A microdeletion at the 8p23 terminal regions of chromosome 8p23 was identified in a Taiwanese patient with ASD, suggesting a potential association with mutations in the DLGAP2 gene. DLGAP2 is expressed in the olfactory bulb in rodents. The current study investigated olfactory phenotypes of Dlgap2 mutant mice. The results indicated that odor detection capabilities were comparable between wild-type (WT) and Dlgap2 mutant mice. However, homozygous mutant (Homo) mice showed less interest in sniffing odors of banana and almond but greater sniffing activity in response to bedding from unfamiliar cages. Notably, exposure to banana odor elicited significant c-fos expression in most olfaction-related brain regions of WT mice, while Homo mice did not show much increase in c-fos levels in major olfactory areas, which may correlate with their diminished sniffing behavior. Bedding stimuli induced pronounced c-fos expression in WT brains and some olfaction-related regions, including the olfactory bulb, amygdala, hypothalamus, and medial prefrontal cortex, in Homo mice. These mutants may still process olfactory signals from the bedding through a relatively narrow channel, which might elicit their interest, leading to increased sniffing behaviors that may compensate for their olfactory deficits. The DLGAP2 protein was absent in the olfactory bulb of Homo mice, and the levels of PSD95 and CaMKIIβ were also affected, indicating alterations in synaptic transmission and signaling within the olfactory system. This study evaluated olfactory perception in a mouse model of ASD, which may advance diagnostic and therapeutic strategies.

Keywords: Autism; C-fos; Mutant mice; Odor stimuli; Olfactory phenotype; Postsynaptic proteins.