title: Mice deficient in CHRNA7, a subunit of the nicotinic acetylcholine receptor, produce sperm with impaired motility.
abstract: In this study we investigate the role of the CHRNA7 subunit (also known as the alpha7 subunit) of the nicotinic acetylcholine receptor in mouse sperm function. We confirm by reverse-transcription-polymerase chain reaction the expression in adult mouse testis of Chrna7 mRNA and demonstrate the subunit's presence in mouse sperm by immunoblot. Alpha-bungarotoxin binds a range of nicotinic acetylcholine receptor subunits, including the CHRNA7 subunit. Localization studies using a fluorescent alpha-bungarotoxin-tetramethyl-rhodamine conjugate revealed specific binding sites on the midpiece of mouse sperm with fainter alpha-bungarotoxin binding on the remainder of the flagellum. Mice engineered with a double-null disruption of the Chrna7 gene displayed only faint fluorescence on the midpiece, suggesting that the CHRNA7 contributed the majority of the observed alpha-bungarotoxin binding sites. The location of alpha-bungarotoxin binding suggested that nicotinic acetylcholine receptors may play an ionotropic role in sperm motility. Sperm from Chrna7(-/-) mice display no difference in number, morphology, viability or spontaneous acrosome reaction rate compared with Chrna7(+/+) sperm. Studies using computer-assisted sperm analysis indicate the motility of Chrna7(-/-) sperm is significantly impaired. This impairment is characterized by significantly reduced swimming velocities, failure to maintain vigorous swimming, and lower levels of hyperactivated swimming patterns in Chrna7(-/-) sperm compared with Chrna7(+/+) sperm. This is the first genetic evidence that sperm nicotinic acetylcholine receptors are important for maintenance of normal sperm motility.
authors.affiliation: Department of Cell Biology and Human Anatomy, School of Medicine, University of California at Davis, 95616-8643, USA. cmbray@ucdavis.edu
authors.forename: Christopher
authors.initials: C
authors.lastname: Bray
authors.forename: Jung-Ho
authors.initials: JH
authors.lastname: Son
authors.forename: Priyadarsini
authors.initials: P
authors.lastname: Kumar
authors.forename: Stanley
authors.initials: S
authors.lastname: Meizel
mesh_terms: D020101:Acrosome Reaction; D000818:Animals; D001835:Body Weight; D002038:Bungarotoxins / Q000378:metabolism; D002470:Cell Survival; D007091:Image Processing, Computer-Assisted; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009929:Organ Size / Q000235:genetics; D011978:Receptors, Nicotinic / Q000172:deficiency* / Q000235:genetics; D013076:Sperm Count; D013081:Sperm Motility; D013737:Testis / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D002038:Bungarotoxins; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor