Targeted deletion of the Kv6.4 subunit causes male sterility due to disturbed spermiogenesis.
Electrically silent voltage-gated potassium (KvS) channel subunits (i.e. Kv5-Kv6 and Kv8-Kv9) do not form functional homotetrameric Kv channels, but co-assemble with Kv2 subunits, generating functional heterotetrameric Kv2--KvS channel complexes in which the KvS subunits modulate the Kv2 channel properties. Several KvS subunits are expressed in testis tissue but knowledge about their contribution to testis physiology is lacking. Here, we report that the targeted deletion of Kv6.4 in a transgenic mouse model (Kcng4-/-) causes male sterility as offspring from homozygous females were only obtained after mating with wild-type (WT) or heterozygous males. Semen quality analysis revealed that the sterility of the homozygous males was caused by a severe reduction in total sperm-cell count and the absence of motile spermatozoa in the semen. Furthermore, spermatozoa of homozygous mice showed an abnormal morphology characterised by a smaller head and a shorter tail compared with WT spermatozoa. Comparison of WT and Kcng4-/-testicular tissue indicated that this inability to produce (normal) spermatozoa was due to disturbed spermiogenesis. These results suggest that Kv6.4 subunits are involved in the regulation of the late stages of spermatogenesis, which makes them a potentially interesting pharmacological target for the development of non-hormonal male contraceptives.
Laboratory of Molecular Biophysics, Physiology and Pharmacology, Department of Biomedical Sciences, University of Antwerp, CDE, Universiteitsplein 1, 2610 Antwerpen, Belgium.
Glenn
G
Regnier
Laboratory of Molecular Biophysics, Physiology and Pharmacology, Department of Biomedical Sciences, University of Antwerp, CDE, Universiteitsplein 1, 2610 Antwerpen, Belgium.
Elke
E
Bocksteins
Laboratory of Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, CDE, Universiteitsplein 1, 2610 Antwerpen, Belgium.
Waleed F
WF
Marei
Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, CGB, Groenenborgerlaan 171, 2020 Antwerpen, Belgium.
Isabel
I
Pintelon
Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, CGB, Groenenborgerlaan 171, 2020 Antwerpen, Belgium.
Jean-Pierre
JP
Timmermans
Laboratory of Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, CDE, Universiteitsplein 1, 2610 Antwerpen, Belgium.
Jo L M R
JLMR
Leroy
Laboratory of Molecular Biophysics, Physiology and Pharmacology, Department of Biomedical Sciences, University of Antwerp, CDE, Universiteitsplein 1, 2610 Antwerpen, Belgium.
Dirk J
DJ
Snyders
D000818:Animals; D048430:Cell Shape / Q000235:genetics; D007248:Infertility, Male / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics* / Q000378:metabolism; D055101:Semen Analysis; D013081:Sperm Motility / Q000235:genetics; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism*; D013737:Testis / Q000378:metabolism*
D024642:Potassium Channels, Voltage-Gated