RNA-sequencing data and whole transcriptome analysis from CDH2 knock-in mice, modeling attention-deficit hyperactivity disorder (ADHD)

Here we demonstrate familial ADHD caused by a missense mutation in CDH2, which encodes the adhesion protein N-cadherin, known to play a significant role in synaptogenesis; In line with the human phenotype, CRISPR/Cas9-mutated knock-in mice harboring the human p.H150Y mutation in the mouse ortholog recapitulated core behavioral features of hyperactivity. Symptoms were modified by methylphenidate, the most commonly prescribed therapeutic for ADHD. The mutated mice exhibited impaired presynaptic vesicle clustering, attenuated evoked transmitter release and decreased spontaneous release. Specific downstream molecular pathways were affected in both the ventral midbrain and prefrontal cortex, with reduced tyrosine hydroxylase expression and dopamine levels. We thus delineate roles for CDH2-related pathways in the pathophysiology of ADHD. Overall design: Prefrontal cortex and ventral mid-brain neuronal mRNA profiles of 16 male 13-week-old wildtype (WT) and CRISPR/Cas9-mutated knock-in mice (harboring the specific human p.H150Y substitution)