ARMC2 loss impairs cilia structure and leads to primary ciliary dyskinesia symptoms in mouse organs

In humans and mice, deficiency in ARMC2 causes Multiple Morphological Abnormalities of the Flagellum (MMAF), a condition defined by absent or aberrant sperm flagella with a disorganized axoneme. Affected men are infertile but with no other obvious signs characteristics/typical for primary cilia dyskinesia (PCD). Given the similarity between cilia and flagella axonemes we investigated a possible role of ARMC2 in cilia functioning. In Armc2 -deficient mice, the length of cilia was reduced in trachea and oviduct. Ciliary beating was also affected, leading to tracheal mucus accumulation and female mutants had fewer pups, likely due to impaired oviductal transport. Additional PCD manifestations included enlarged brain ventricles and occasional severe hydrocephalus, and situs ambiguus were also observed. Altogether, these findings suggest that mutations of ARMC2 might be also a molecular cause of human PCD.