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Catsper3 and Catsper4 Are Essential for Sperm Hyperactivated Motility and Male Fertility in the Mouse¹

Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557

ABSTRACT

Catsper3 and Catsper4 are two recently identified testis-specific genes homologous to Catsper1 and Catsper2 that have been shown to play an essential role in sperm hyperactivated motility and male fertility in mice. Here we report that Catsper3 and Catsper4 knockout male mice are completely infertile due to a quick loss of motility and a lack of hyperactivated motility under capacitating conditions. Our data demonstrate that both CATSPER3 and CATSPER4 are required for hyperactivated sperm motility during capacitation and for male fertility. The present study also demands a revisit to the idiopathic male infertility patients who show normal sperm counts and normal initial motility for defects in sperm hyperactivated motility and for potential CATSPER gene mutations. The CATSPER channel also may be an excellent drug target for male contraceptives.

fertilization, infertility, ion channel, sperm, spermatogenesis, sperm capacitation, sperm maturation, sperm motility and transport, testis

³These authors contributed equally to this work.

¹Supported by a start-up fund from the University of Nevada, Reno, and also in part by National Institutes of Health grant HD050281 to W.Y.

³These authors contributed equally to this work.

Correspondence: ²Wei Yan, Department of Physiology and Cell Biology, University of Nevada School of Medicine, 1664 North Virginia St., MS 352, Reno, NV 89557. FAX: 775 784 6903; e-mail: wyan{at}unr.edu

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