TY - JOUR
T1 - Highly demarcated structural alterations in the brain and impaired social incentive learning in Tbx1 heterozygous mice
AU - Hiramoto, Takeshi
AU - Sumiyoshi, Akira
AU - Kato, Risa
AU - Yamauchi, Takahira
AU - Takano, Takeshi
AU - Kang, Gina
AU - Esparza, Marisa
AU - Matsumura, Bailey
AU - Stevens, Lucas J.
AU - Hiroi, Yukiko J.
AU - Tanifuji, Takaki
AU - Ryoke, Rie
AU - Nonaka, Hiroi
AU - Machida, Akihiro
AU - Nomoto, Kensaku
AU - Mogi, Kazutaka
AU - Kikusui, Takefumi
AU - Kawashima, Ryuta
AU - Hiroi, Noboru
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024
Y1 - 2024
N2 - Copy number variants (CNVs) are robustly associated with psychiatric disorders and changes in brain structures. However, because CNVs contain many genes, the precise gene-phenotype relationship remains unclear. Although various volumetric alterations in the brains of 22q11.2 CNV carriers have been identified in humans and mouse models, it is unknown how each gene encoded in the 22q11.2 region contributes to structural alterations, associated mental illnesses, and their dimensions. Our previous studies identified Tbx1, a T-box family transcription factor encoded in the 22q11.2 CNV, as a driver gene for social interaction and communication, spatial and working memory, and cognitive flexibility. However, it remains unclear how TBX1 impacts the volumes of various brain regions and their functionally linked behavioral dimensions. In this study, we used volumetric magnetic resonance imaging analysis to comprehensively evaluate brain region volumes and behavioral alterations relevant to affected structures in congenic Tbx1 heterozygous mice. Our data showed that the volumes of the anterior and posterior portions of the amygdaloid complex and its surrounding cortical regions were most robustly reduced in Tbx1 heterozygous mice. In an amygdala-dependent task, Tbx1 heterozygous mice were impaired in their ability to learn the incentive value of a social partner. The volumes of the primary and secondary auditory cortexes were increased, and acoustic, but not non-acoustic, sensorimotor gating was impaired in Tbx1 heterozygous mice. Our findings identify the brain’s regional volume alterations and their relevant behavioral dimensions associated with Tbx1 heterozygosity.
AB - Copy number variants (CNVs) are robustly associated with psychiatric disorders and changes in brain structures. However, because CNVs contain many genes, the precise gene-phenotype relationship remains unclear. Although various volumetric alterations in the brains of 22q11.2 CNV carriers have been identified in humans and mouse models, it is unknown how each gene encoded in the 22q11.2 region contributes to structural alterations, associated mental illnesses, and their dimensions. Our previous studies identified Tbx1, a T-box family transcription factor encoded in the 22q11.2 CNV, as a driver gene for social interaction and communication, spatial and working memory, and cognitive flexibility. However, it remains unclear how TBX1 impacts the volumes of various brain regions and their functionally linked behavioral dimensions. In this study, we used volumetric magnetic resonance imaging analysis to comprehensively evaluate brain region volumes and behavioral alterations relevant to affected structures in congenic Tbx1 heterozygous mice. Our data showed that the volumes of the anterior and posterior portions of the amygdaloid complex and its surrounding cortical regions were most robustly reduced in Tbx1 heterozygous mice. In an amygdala-dependent task, Tbx1 heterozygous mice were impaired in their ability to learn the incentive value of a social partner. The volumes of the primary and secondary auditory cortexes were increased, and acoustic, but not non-acoustic, sensorimotor gating was impaired in Tbx1 heterozygous mice. Our findings identify the brain’s regional volume alterations and their relevant behavioral dimensions associated with Tbx1 heterozygosity.
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U2 - 10.1038/s41380-024-02797-x
DO - 10.1038/s41380-024-02797-x
M3 - Article
C2 - 39463450
AN - SCOPUS:85207366591
SN - 1359-4184
JO - Molecular psychiatry
JF - Molecular psychiatry
ER -