Sperm-Associated Antigen–17 Gene Is Essential for Motile Cilia Function and Neonatal Survival

• DOI: 10.1165/rcmb.2012-0362oc
• Publication Date: 2013-02-16T03:23:49Z
• Authors: Maria Eugenia Teves; Zhibing Zhang; Richard M. Costanzo; Scott C. Henderson; Frank D. Corwin; Jamal Zweit; Gobalakrishnan Su...; Mark Subler; Fadi N. Salloum; Bruce K. Rubin; Jerome F. Strauss
• Keywords: Motile cilium; Intraflagellar Transport; Mucociliary clearance; Video microscopy

Primary ciliary dyskinesia (PCD), resulting from defects in cilia assembly or motility, is caused by mutations a number of genes encoding axonemal proteins. PCD phenotypes are variable, and include recurrent respiratory tract infections, bronchiectasis, hydrocephaly, situs inversus, male infertility. We generated knockout mice for the sperm-associated antigen-17 (Spag17) gene, which encodes central pair (CP) protein present axonemes cells with "9 + 2" motile flagella. The targeting Spag17 resulted severe phenotype characterized immotile nasal tracheal cilia, reduced clearance mucus, profound distress associated lung fluid accumulation disruption alveolar epithelium, cerebral ventricular expansion consistent emerging hydrocephalus, failure to suckle, neonatal demise within 12 hours birth. Ultrastructural analysis revealed loss one CP microtubule approximately quarter axonemes, an absence C1 projection, other less frequent structural abnormalities. SPAG6 SPAG16 (CP proteins that interact SPAG17) were increased tissue SPAG17-deficient mice. conclude plays critical role function structure lethality likely explained impaired airway mucociliary clearance.