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Chunk #7 — RESULTS — Expression and developmental regulation of NHE9 in brain

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Functional evaluation of autism-associated mutations in NHE9.
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In the wake of the association of NHE9 with autism we sought to investigate the spatiotemporal distribution of NHE9 in the developing and adult mouse brain. Although no single region of the brain has yet been clearly identified as being associated with autism, two decades of magnetic resonance imaging (MRI) studies have implicated cerebellum, frontal cortex, hippocampus and amygdala. Postmortem findings, animal models, and neuroimaging studies further strengthen these observations39,40. In-situ hybridization data of the adult mouse brain obtained from the Allen Brain Atlas41 indicate that the expression levels of NHE9 are highest in the cortex (~27% of total NHE9 expression in the brain), hippocampus (~30%) and the olfactory lobes (~50%) (Figure 4A) compared to the other regions of the brain. Variations of gene expression in the brain may play a crucial role in the behavioral phenotypes observed in autism and suggest a strong association with the cortex, which is the seat of memory, attention, thought, language, and consciousness in the brain. Recent reports comparing autistic and control brains suggested an attenuation of normal differential gene expression between frontal and