LAUSR

Background The 15q13.3 microdeletion syndrome is caused by a 1.5 MB hemizygous microdeletion at chromosome 15q13.3 affecting seven genes: FAN1, MTMR10, TRPM1, MIR211, KLF13, OTUD7A, and CHRNA7. The 15q13.3 microdeletion increases the risk of intellectual disability, epilepsy, autism spectrum disorder and schizophrenia, though the clinical profile varies considerably. Mouse models of the 15q13.3 microdeletion recapitulate a number of the behavioral and physiological deficits that characterize the human condition. Still, little is known of the underlying biological mechanisms. Methods We have performed RNA sequencing (RNA-seq) of five brain areas, frontal cortex, striatum, parietal cortex, hippocampus and cerebellum from 15q13.3 homozygous knockout mice and wild type littermates, with an average of 9 samples per group. Results Our transcriptomic analysis identified about 100 genes that were differentially expressed in 15q13.3 homozygous knockout mice compared to wildtype littermates after correction for multiple testing. The majority of these genes were regulated in the same direction in hemizygous 15q13.3 deletion mice, indicating that the changes we see are also relevant for the hemizygous deletion syndrome. Discussion Further investigation of the biological functions affected by these transcriptional changes can guide target identification and drug discovery efforts for intellectual disability, epilepsy, autism spectrum disorder and schizophrenia.