Haploinsufficiency of autism causative gene Tbr1 impairs olfactory discrimination and neuronal activation of the olfactory system in mice

Molecular Autism
Tzyy-Nan HuangYi-Ping Hsueh

Abstract

Autism spectrum disorders (ASD) exhibit two clusters of core symptoms, i.e., social and communication impairment, and repetitive behaviors and sensory abnormalities. Our previous study demonstrated that TBR1, a causative gene of ASD, controls axonal projection and neuronal activation of amygdala and regulates social interaction and vocal communication in a mouse model. Behavioral defects caused by Tbr1 haploinsufficiency can be ameliorated by increasing neural activity via D-cycloserine treatment, an N-methyl-D-aspartate receptor (NMDAR) coagonist. In this report, we investigate the role of TBR1 in regulating olfaction and test whether D-cycloserine can also improve olfactory defects in Tbr1 mutant mice. We used Tbr1 +/- mice as a model to investigate the function of TBR1 in olfactory sensation and discrimination of non-social odors. We employed a behavioral assay to characterize the olfactory defects of Tbr1 +/- mice. Magnetic resonance imaging (MRI) and histological analysis were applied to characterize anatomical features. Immunostaining was performed to further analyze differences in expression of TBR1 subfamily members (namely TBR1, TBR2, and TBX21), interneuron populations, and dendritic abnormalities in olfactory bulbs...Continue Reading

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Citations

Apr 11, 2020·European Journal of Human Genetics : EJHG·Sophie NambotWilliam B Dobyns
Apr 11, 2020·European Journal of Human Genetics : EJHG·Yi-Ping HsuehTzyy-Nan Huang
Jun 26, 2020·Journal of Neurodevelopmental Disorders·Nicole Martin-Kenny, Nathalie G Bérubé
Sep 20, 2020·Human Genomics·Laurie-Anne Sapey-TriomphePatrick Edery
Jul 15, 2020·Translational Psychiatry·Sheema HashemMohammad Haris
Apr 23, 2020·Frontiers in Cell and Developmental Biology·Rui XiaoXiaotang Fan
Dec 11, 2020·Scientific Reports·L Pérez-RevueltaJ R Alonso
May 13, 2021·Seminars in Cell & Developmental Biology·Janardhan P BhattaraiMinghong Ma

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