Gastrointestinal dysfunction in autism displayed by altered motility and achalasia in Foxp1 ^+/− mice

Significance Gastrointestinal symptoms are common in patients with autism spectrum disorder (ASD), yet are poorly understood. To further dissect this phenomenon, we investigated a mouse model mimicking the haploinsufficiency seen in patients with FOXP1 syndrome. We found a disturbed structure and function of the gastrointestinal system, atrophy and malfunction of the tunica muscularis, esophageal achalasia, and increased total transit based on altered colon motility. Furthermore, Foxp1 target genes identified in the brain were dysregulated in the Foxp1 +/− esophagus. Our findings support the idea that genes relevant in brain function might also cause gastrointestinal disturbances in ASD patients and that these primary defects deserve appropriate treatment.