1. Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School, Enders 1309, 320 Longwood Avenue, Boston, Massachusetts 02115, USA
2. Vincent Center for Reproductive Biology, Massachusetts General Hospital and Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, Massachusetts 02114, USA

Correspondence to: David E. Clapham¹ Correspondence and requests for materials should be addressed to D.E.C. (e-mail: Email: dclapham@rascal.med.harvard.edu). The GenBank accession numbers are AF407332 for mouse CatSper and AF407333 for human CatSper.

Abstract

Calcium and cyclic nucleotides have crucial roles in mammalian fertilization, but the molecules comprising the Ca²⁺-permeation pathway in sperm motility are poorly understood. Here we describe a putative sperm cation channel, CatSper, whose amino-acid sequence most closely resembles a single, six-transmembrane-spanning repeat of the voltage-dependent Ca²⁺-channel four-repeat structure. CatSper is located specifically in the principal piece of the sperm tail. Targeted disruption of the gene results in male sterility in otherwise normal mice. Sperm motility is decreased markedly in CatSper^-/- mice, and CatSper^-/- sperm are unable to fertilize intact eggs. In addition, the cyclic-AMP-induced Ca²⁺ influx is abolished in the sperm of mutant mice. CatSper is thus vital to cAMP-mediated Ca²⁺ influx in sperm, sperm motility and fertilization. CatSper represents an excellent target for non-hormonal contraceptives for both men and women.