A novel mouse model recapitulates features of the neurodevelopmental disorder 3p25.3 microdeletion syndrome

Neurodevelopmental disorders globally affect approximately 15% of children and adolescents, but many disorders do not have mouse models, thus limiting our ability to further understand them and ultimately develop treatments. In our study, we developed a novel mouse line to model 3p25.3 microdeletion syndrome (6qE3del/+) that reliably recapitulates key features of the syndrome. 6qE3del/+ mice display congenital heart defects, craniofacial defects, skeletal anomalies and subtle brain changes. We also generated another neurodevelopmental disorder model for a gene often included in the deleted region, Brpf1, and found that congenital heart defects and craniofacial defects may be partly attributable to the heterozygous loss of Brpf1 in 6qE3del/+ mice. Together our work offers new neurodevelopment models, and provides evidence that treatments developed for Brpf1 haploinsufficiency may also benefit 3p25.3 microdeletion syndrome.