Brain transcriptome analysis of Myt1l heterozygote mutation mice in different brain regions (RNA-Seq II)

Myt1l, a zinc-finger transcription factor, promotes neuronal differentiation and is implicated in autism spectrum disorders (ASD) and intellectual disability. However, it was previously unclear whether Myt1l promotes neuronal differentiation in vivo, how its deficiency leads to disease-related mouse phenotypes, and whether and how ASD-risk genes with strong embryonic and perinatal gene expression can yield strong adult-stage ASD-related phenotypes. Here, we report that Myt1l-heterozygous knockout (Myt1l-HT) mice display postnatal age-differential ASD-like phenotypes: Newborn Myt1l-HT mice show ASD-like transcriptomic changes involving suppressed neuronal and synaptic gene expression and suppressed right reflex. Juvenile Myt1l-HT mice display mixed ASD-like and reverse-ASD transcriptomic patterns and large normal behaviors, accompanying increased prefrontal excitatory synaptic transmission. However, adult Myt1l-HT mice show additional ASD-like transcriptomic changes involving astrocytic and microglial genes, along with behavioral deficits and excessive prefrontal inhibitory synaptic transmission. Therefore, Myt1l HT leads to newborn-stage ASD-like neuronal suppression, temporary juvenile normalization, and subsequent adult-stage ASD-like deficits. Overall design: Sub-brain transcriptome of Myt1l heterozygote mutation mice in prefrontal cortex, hippocampus, and striatum