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- W4286256912 endingPage "104800" @default.
- W4286256912 startingPage "104800" @default.
- W4286256912 abstract "The human vesicular monoamine transporter 1 (VMAT1) harbors unique substitutions (Asn136Thr/Ile) that affect monoamine uptake into synaptic vesicles. These substitutions are absent in all known mammals, suggesting their contributions to distinct aspects of human behavior modulated by monoaminergic transmissions, such as emotion and cognition. To directly test the impact of these human-specific mutations, we introduced the humanized residues into mouse Vmat1 via CRISPR/Cas9-mediated genome editing and examined changes at the behavioral, neurophysiological, and molecular levels. Behavioral tests revealed reduced anxiety-related traits of Vmat1Ile mice, consistent with human studies, and electrophysiological recordings showed altered oscillatory activity in the amygdala under anxiogenic conditions. Transcriptome analyses further identified changes in gene expressions in the amygdala involved in neurodevelopment and emotional regulation, which may corroborate the observed phenotypes. This knock-in mouse model hence provides compelling evidence that the mutations affecting monoaminergic signaling and amygdala circuits have contributed to the evolution of human socio-emotional behaviors." @default.
- W4286256912 created "2022-07-21" @default.
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- W4286256912 date "2022-08-01" @default.
- W4286256912 modified "2023-10-14" @default.
- W4286256912 title "Humanized substitutions of Vmat1 in mice alter amygdala-dependent behaviors associated with the evolution of anxiety" @default.
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