Although twin studies indicate clear genetic bases of autism spectrum disorder 
(ASD), the precise mechanisms through which genetic variations causally result 
in ASD are poorly understood. Individuals with 3 Mb and nested 1.5 Mb 
hemizygosity of the chromosome 22q11.2 represent genetically identifiable cases 
of ASD. However, because more than 30 genes are deleted even in the minimal 
deletion cases of 22q11.2 deficiency, the individual 22q11.2 gene(s) responsible 
for ASD remain elusive. Here, we examined the impact of constitutive 
heterozygosity of Tbx1, a 22q11.2 gene, on the behavioral phenotypes of ASD and 
characterized the regional and cellular expression of its mRNA and protein in 
mice. Congenic Tbx1 heterozygous (HT) mice were impaired in social interaction, 
ultrasonic vocalization, memory-based behavioral alternation, working memory and 
thigmotaxis, compared with wild-type (WT) mice. These phenotypes were not due to 
non-specific alterations in olfactory function, exploratory behavior, motor 
movement or anxiety-related behavior. Tbx1 mRNA and protein were ubiquitously 
expressed throughout the brains of C57BL/6J mice, but protein expression was 
enriched in regions that postnatally retain the capacity of neurogenesis, and in 
fact, postnatally proliferating cells expressed Tbx1. In postnatally derived 
hippocampal culture cells of C57BL/6J mice, Tbx1 levels were higher during 
proliferation than during differentiation, and expressed in neural progenitor 
cells, immature and matured neurons and glial cells. Taken together, our data 
suggest that Tbx1 is a gene responsible for the phenotypes of 22q11.2 
hemizygosity-associated ASD possibly through its role in diverse cell types, 
including postnatally and prenatally generated neurons.