• PMID: 22654668
• Gene Name: KATNAL1
• Condition: Essential for spermiogenesis, Mal einfertility
• Association: Associated
• Sex: Male
• Infertility type: Male ifertility
• Other associated phenotypes: Essential for spermiogenesis, Mal einfertility

KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility

Smith LB, Milne L, Nelson N, Eddie S, Brown P, Atanassova N, O'Bryan MK, O'Donnell L, Rhodes D, Wells S, Napper D, Nolan P, Lalanne Z, Cheeseman M, Peters J.

Spermatogenesis is a complex process reliant upon interactions between germ cells (GC) and supporting somatic cells. Testicular Sertoli cells (SC) support GCs during maturation through physical attachment, the provision of nutrients, and protection from immunological attack. This role is facilitated by an active cytoskeleton of parallel microtubule arrays that permit transport of nutrients to GCs, as well as translocation of spermatids through the seminiferous epithelium during maturation. It is well established that chemical perturbation of SC microtubule remodelling leads to premature GC exfoliation demonstrating that microtubule remodelling is an essential component of male fertility, yet the genes responsible for this process remain unknown. Using a random ENU mutagenesis approach, we have identified a novel mouse line displaying male-specific infertility, due to a point mutation in the highly conserved ATPase domain of the novel KATANIN p60-related microtubule severing protein Katanin p60 subunit A-like1 (KATNAL1). We demonstrate that Katnal1 is expressed in testicular Sertoli cells (SC) from 15.5 days post-coitum (dpc) and that, consistent with chemical disruption models, loss of function of KATNAL1 leads to male-specific infertility through disruption of SC microtubule dynamics and premature exfoliation of spermatids from the seminiferous epithelium. The identification of KATNAL1 as an essential regulator of male fertility provides a significant novel entry point into advancing our understanding of how SC microtubule dynamics promotes male fertility. Such information will have resonance both for future treatment of male fertility and the development of non-hormonal male contraceptives. FAU - Smith, Lee B AU - Smith LB AD - MRC Centre for Reproductive Health, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh, United Kingdom. Lee.Smith@ed.ac.uk FAU - Milne, Laura AU - Milne L FAU - Nelson, Nancy AU - Nelson N FAU - Eddie, Sharon AU - Eddie S FAU - Brown, Pamela AU - Brown P FAU - Atanassova, Nina AU - Atanassova N FAU - O'Bryan, Moira K AU - O'Bryan MK FAU - O'Donnell, Liza AU - O'Donnell L FAU - Rhodes, Danielle AU - Rhodes D FAU - Wells, Sara AU - Wells S FAU - Napper, Diane AU - Napper D FAU - Nolan, Patrick AU - Nolan P FAU - Lalanne, Zuzanna AU - Lalanne Z FAU - Cheeseman, Michael AU - Cheeseman M