title: Hspa4l-deficient mice display increased incidence of male infertility and hydronephrosis development.
abstract: The Hspa4l gene, also known as Apg1 or Osp94, belongs to the HSP110 heat shock gene family, which includes three genes encoding highly conserved proteins. This study shows that Hspa4l is expressed ubiquitously and predominantly in the testis. The protein is highly expressed in spermatogenic cells, from late pachytene spermatocytes to postmeiotic spermatids. In the kidney, the protein is restricted to cortical segments of distal tubules. To study the physiological role of this gene in vivo, we generated mice deficient in Hspa4l by gene targeting. Hspa4l-deficient mice were born at expected ratios and appeared healthy. However, approximately 42% of Hspa4l(-/-) male mice suffered from fertility defects. Whereas the seminiferous tubules of Hspa4l(-/-) testes contained all stages of germ cells, the number of mature sperm in the epididymis and sperm motility were drastically reduced. The reduction of the sperm count was due to the elimination of a significant number of developing germ cells via apoptosis. No defects in fertility were observed in female mutants. In addition, 12% of null mutant mice developed hydronephrosis. Concentrations of plasma and urine electrolytes in Hspa4l(-/-) mice were similar to wild-type values, suggesting that the renal function was not impaired. However, Hspa4l(-/-) animals were preferentially susceptible to osmotic stress. These results provide evidence that Hspa4l is required for normal spermatogenesis and suggest that Hspa4l plays a role in osmotolerance.
authors.affiliation: Institute of Human Genetics, University of Göttingen, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Held
authors.forename: Ilona
authors.initials: I
authors.lastname: Paprotta
authors.forename: Janchiv
authors.initials: J
authors.lastname: Khulan
authors.forename: Bernhardt
authors.initials: B
authors.lastname: Hemmerlein
authors.forename: Lutz
authors.initials: L
authors.lastname: Binder
authors.forename: Stephan
authors.initials: S
authors.lastname: Wolf
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schubert
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinhardt
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Engel
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: Adham
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D005260:Female; D018390:Gene Targeting; D005854:Germ Cells / Q000166:cytology / Q000502:physiology; D050957:HSP110 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006869:Hydronephrosis / Q000235:genetics / Q000378:metabolism*; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009994:Osmolar Concentration; D011247:Pregnancy; D012098:Reproduction / Q000235:genetics / Q000502:physiology; D013091:Spermatogenesis / Q000502:physiology; D013094:Spermatozoa / Q000166:cytology / Q000502:physiology; D013737:Testis / Q000166:cytology / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C485680:Hspa4 protein, mouse