PT  - JOURNAL ARTICLE
AU  - Jeffrey H. Kogan
AU  - Adam K. Gross
AU  - Robert E. Featherstone
AU  - Rick Shin
AU  - Qian Chen
AU  - Carrie L. Heusner
AU  - Megumi Adachi
AU  - Amy Lin
AU  - Noah M. Walton
AU  - Sosuke Miyoshi
AU  - Shinichi Miyake
AU  - Katsunori Tajinda
AU  - Hiroyuki Ito
AU  - Steven J. Siegel
AU  - Mitsuyuki Matsumoto
TI  - Mouse Model of Chromosome 15q13.3 Microdeletion Syndrome Demonstrates Features Related to Autism Spectrum Disorder
AID  - 10.1523/JNEUROSCI.3967-14.2015
DP  - 2015 Dec 09
TA  - The Journal of Neuroscience
PG  - 16282--16294
VI  - 35
IP  - 49
4099  - http://www.jneurosci.org/content/35/49/16282.short
4100  - http://www.jneurosci.org/content/35/49/16282.full
SO  - J. Neurosci.2015 Dec 09; 35
AB  - 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 microdeletion in humans results in a range of neurodevelopmental/psychiatric disorders, including epilepsy, intellectual disability, schizophrenia, and autism spectrum disorder (ASD). The disorders conferred by a 15q13.3 microdeletion also have overlapping genetic architectures and comorbidity in other patient populations such as those with epilepsy and schizophrenia/psychosis, as well as schizophrenia and ASD. We generated mice carrying a deletion of 1.2 Mb homologous to the 15q13.3 microdeletion in human patients, which allowed us to investigate the potential causes of neurodevelopmental/psychiatric disorders associated with the CNV.