Keywords :
Alternative Splicing; Animals; Blotting, Northern; Blotting, Southern; Blotting, Western; Calcium/metabolism; Calcium-Transporting ATPases/biosynthesis; Cation Transport Proteins; Cloning, Molecular; DNA, Complementary/metabolism; Fertility; Fertilization in Vitro; Fluoresceins/pharmacology; Fluorescent Dyes/pharmacology; Genotype; Humans; Male; Mice; Mice, Knockout; Microscopy, Fluorescence; Models, Genetic; Molecular Sequence Data; Plasma Membrane Calcium-Transporting ATPases; Protein Isoforms; Protein Structure, Tertiary; Rats; Recombination, Genetic; Reverse Transcriptase Polymerase Chain Reaction; Sperm Motility; Succinimides/pharmacology; Testis/metabolism; Time Factors
Abstract :
[en] Calcium and Ca(2+)-dependent signals play a crucial role in sperm motility and mammalian fertilization, but the molecules and mechanisms underlying these Ca(2+)-dependent pathways are incompletely understood. Here we show that homozygous male mice with a targeted gene deletion of isoform 4 of the plasma membrane calcium/calmodulin-dependent calcium ATPase (PMCA), which is highly enriched in the sperm tail, are infertile due to severely impaired sperm motility. Furthermore, the PMCA inhibitor 5-(and-6)-carboxyeosin diacetate succinimidyl ester reduced sperm motility in wild-type animals, thus mimicking the effects of PMCA4 deficiency on sperm motility and supporting the hypothesis of a pivotal role of the PMCA4 on the regulation of sperm function and intracellular Ca(2+) levels.
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