The Ciliary GTPase ARL13B maintains Ductule Physiology through the Primary and Motile Cilia in Male Reproduction

ARL13B is a small regulatory GTPase that controls ciliary membrane composition in both motile cilia and non-motile primary cilia. In this study, we investigated the role of ARL13B in the efferent ductules, tubules of the male reproductive tract essential to male fertility in which primary and motile cilia co-exist. We used a genetically engineered mouse model to deleteArl13bin efferent ductule epithelial cells, resulting in compromised primary and motile cilia architecture and functions. This deletion led to disturbances in reabsorptive/secretory processes and triggered an inflammatory response. The observed male reproductive phenotype showed significant variability linked to partial infertility, highlighting the importance of ARL13B in maintaining a proper physiological balance in these small ducts. These results emphasize the dual role of both motile and primary cilia functions in regulating efferent duct homeostasis, offering deeper insights into how cilia related diseases affect the male reproductive system. Overall design: To investigate the function of Arl13b in efferent ductules physiology and male fertility we established a conditionnal Knock Out mice of Arl13b using the Cre lox system to specifically ablated Arl13b following the expression of cre recombinase under the promotor of Villin. We then performed gene expression profiling analysis using efferent ductules of 5 differents mice for each control and cKO.