Inactivation of Nxf2 causes defects in male meiosis and age-dependent depletion of spermatogonia.
In eukaryotes, mRNA is actively transported from nucleus to cytoplasm by a family of nuclear RNA export factors (NXF). While yeast harbors only one such factor (Mex67p), higher eukaryotes encode multiple NXFs. In mouse, four Nxf genes have been identified: Nxf1, Nxf2, Nxf3, and Nxf7. To date, the function of mouse Nxf genes has not been studied by targeted gene deletion in vivo. Here we report the generation of Nxf2 null mutant mice by homologous recombination in embryonic stem cells. Nxf2-deficient male mice exhibit fertility defects that differ between mouse strains. One third of Nxf2-deficient males on a mixed (C57BL/6x129) genetic background exhibit meiotic arrest and thus are sterile, whereas the remaining males are fertile. Disruption of Nxf2 in inbred (C57BL/6J) males impairs spermatogenesis, resulting in male subfertility, but causes no meiotic arrest. Testis weight and sperm output in C57BL/6J Nxf2(-/Y) mice are sharply reduced. Mutant epididymal sperm exhibit diminished motility. Importantly, proliferation of spermatogonia in Nxf2(-/Y) mice is significantly decreased. As a result, inactivation of Nxf2 causes depletion of germ cells in a substantial fraction of seminiferous tubules in aged mice. These studies demonstrate that Nxf2 plays a dual function in spermatogenesis: regulation of meiosis and maintenance of spermatogonial stem cells.
Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA.
Jieyan
J
Pan
Sigrid
S
Eckardt
N Adrian
NA
Leu
Mariano G
MG
Buffone
Jian
J
Zhou
George L
GL
Gerton
K John
KJ
McLaughlin
Peijing Jeremy
PJ
Wang
D000367:Age Factors; D000818:Animals; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D008297:Male; D008540:Meiosis; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics* / Q000378:metabolism; D034443:RNA Transport; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D013081:Sperm Motility / Q000235:genetics; D013091:Spermatogenesis / Q000235:genetics; D013093:Spermatogonia / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*
D029543:Nucleocytoplasmic Transport Proteins; C502321:Nxf2 protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins