The type 3 adenylyl cyclase is crucial for intestinal mucosal neural network in the gut lamina propria

Abstract Background The type 3 adenylyl cyclase (AC3) enzyme is involved in the synthesis of cyclic adenosine monophosphate (cAMP). It is primarily expressed in the central nervous system (CNS) and plays a crucial role in neurogenesis and neural dendritic arborization. However, the AC3’s functional role in the gastrointestinal tract remains ambiguous. Methods AC3 expression in enteric tissue of AC3 +/+ mice was investigated using immunohistochemistry and RT‐PCR. AC3 knock‐out mice (AC3 −/− ) were used to examine the effect of AC3 on the enteric nervous system (ENS) function and the number of cilia and apoptotic cells. Additionally, total gastrointestinal transit time and colonic motility were compared between the AC3 −/− and AC3 +/+ groups of mice. Key Results AC3 was predominately expressed in the myenteric plexus of the large intestine. Colonic‐bead expulsion analysis showed accelerated propulsion in the large intestine of the AC3 −/− mice. The AC3 −/− mice demonstrated reduced nerve fibers and enteric glial cells count in colonic mucosa compared to the AC3 +/+ mice. Furthermore, AC3 −/− mice exhibited increased cellular apoptosis and reduced ARL13B + cilium cells in the colonic lamina propria compared to the AC3 +/+ mice. Conclusions In AC3 −/− mice, innervation of the lamina propria in the colonic mucosa was reduced and colonic propulsion was accelerated. AC3 is crucial for the development and function of the adult neural network of ENS. AC3 deficiency caused atrophy in the colonic mucosal neural network of mice.