Disruption of the murine dynein light chain gene Tcte3-3 results in asthenozoospermia.
To elucidate the role of the mouse gene Tcte3 (Tctex2), which encodes a putative light chain of the outer dynein arm of cilia and sperm flagella, we have inactivated this gene in mice using targeted disruption. Breeding of heterozygous males and females resulted in normal litter size; however, we were not able to detect homozygous Tcte3-deficent mice using standard genotype techniques. In fact, our results indicate the presence of at least three highly similar copies of the Tcte3 gene (Tcte3-1, Tcte3-2, and Tcte3-3) in the murine genome. Therefore, quantitative real-time PCR was established to differentiate between mice having one or two targeted Tcte3-3 alleles. By this approach, Tcte3-3(-/-) animals were identified, which were viable and revealed no obvious malformation. Interestingly, some homozygous Tcte3-3-deficient male mice bred with wild-type female produced no offspring while other Tcte3-3-deficient males revealed decreased sperm motility but were fertile. In infertile Tcte3-3(-/-) males, spermatogenesis was affected and sperm motility was reduced, too, resulting in decreased ability of Tcte3-3-deficient spermatozoa to move from the uterus into the oviduct. Impaired flagellar motility is not correlated with any gross defects in the axonemal structure, since outer dynein arms are detectable in sperm of Tcte3-3(-/-) males. However, in infertile males, deficient Tcte3-3 function is correlated with increased apoptosis during male germ cell development, resulting in a reduction of sperm number. Moreover, multiple malformations in developing haploid germ cells are present. Our results support a role of Tcte3-3 in generation of sperm motility as well as in male germ cell differentiation.
Rashid
Sajid
S
Institute of Human Genetics, University of Goettingen, 37073 Goettingen, Germany.
Grzmil
Pawel
P
Drenckhahn
Joerg-Detlef
JD
Meinhardt
Andreas
A
Adham
Ibrahim
I
Engel
Wolfgang
W
Neesen
Juergen
J
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D053627:Asthenozoospermia / Q000235:genetics* / Q000503:physiopathology*; D004398:Dyneins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004822:Epididymis / Q000473:pathology; D005187:Fallopian Tubes / Q000502:physiology; D005260:Female; D018390:Gene Targeting / Q000379:methods; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000235:genetics; D013076:Sperm Count; D013077:Sperm Head / Q000473:pathology; D013081:Sperm Motility / Q000235:genetics; D013082:Sperm Tail / Q000378:metabolism / Q000473:pathology; D013083:Sperm Transport; D013091:Spermatogenesis / Q000235:genetics; D013094:Spermatozoa / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000378:metabolism / Q000473:pathology; D014599:Uterus / Q000502:physiology; D014617:Vacuoles / Q000473:pathology
D020033:Protein Isoforms; C533389:Tcte3 protein, mouse; D004398:Dyneins