Mouse Model of Chromosome 15q13.3 Microdeletion Syndrome Demonstrates Features Related to Autism Spectrum Disorder

作者：Jeffrey H. Kogan, Adam K. Gross, Robert E. Featherstone, Rick Shin, Qian Chen, Carrie Heusner, Megumi Adachi, Amy Lin, Noah M. Walton, Sosuke Miyoshi, Shinichi Miyake, Katsunori Tajinda, Hiroyuki Ito, Steven J. Siegel, Mitsuyuki Matsumoto · 发表于：Journal of Neuroscience · 年份：2015 · DOI：10.1523/jneurosci.3967-14.2015 · 被引用次数：61 · 研究领域：Genomic variations and chromosomal abnormalities、Congenital heart defects research、Autism Spectrum Disorder Research

The chromosome 15q13.3 microdeletion is a pathogenic copy number variation conferring epilepsy, intellectual disability, schizophrenia, and autism spectrum disorder (ASD). We generated mice carrying a deletion of 1.2 Mb homologous to the 15q13.3 microdeletion in human patients. Here, we report that mice with a heterozygous deletion on a C57BL/6 background (D/+ mice) demonstrated phenotypes including enlarged/heavier brains (macrocephaly) with enlarged lateral ventricles, decreased social interactions, increased repetitive grooming behavior, reduced ultrasonic vocalizations, decreased auditory-evoked gamma band EEG, and reduced event-related potentials. D/+ mice had normal body weight, activity levels, sensory gating, and cognitive abilities and no signs of epilepsy/seizures. Our results demonstrate that D/+ mice represent ASD-related phenotypes associated with 15q13.3 microdeletion syndrome. Further investigations using this chromosome-engineered mouse model may uncover the common mechanism(s) underlying ASD and other neurodevelopmental/psychiatric disorders representing the 15q13.3 microdeletion syndrome, including epilepsy, intellectual disability, and schizophrenia. SIGNIFICANCE STATEMENT: Recently discovered pathologic copy number variations (CNVs) from patients with neurodevelopmental/psychiatric disorders show very strong penetrance and thus are excellent candidates for mouse models of disease that can mirror the human genetic conditions with high fidelity. A 15q13.3 mi...