Open AccessHspa4l-Deficient Mice Display Increased Incidence of Male Infertility and Hydronephrosis Development
Author(s) -
Torsten Held,
Ilona Paprotta,
Janchiv Khulan,
Bernhardt Hemmerlein,
Lutz Binder,
Stephan Wolf,
Stephanie Schubert,
Andreas Meinhardt,
Wolfgang Engel,
Ibrahim M. Adham
Publication year - 2006
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.01332-06
Subject(s) - biology , spermatogenesis , sperm , male infertility , andrology , epididymis , gene , sperm motility , mutant , medicine , azoospermia , endocrinology , genetics , microbiology and biotechnology , infertility , pregnancy
TheHspa4l gene, also known asApg1 orOsp94 , belongs to the HSP110 heat shock gene family, which includes three genes encoding highly conserved proteins. This study shows thatHspa4l 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% ofHspa4l −/− male mice suffered from fertility defects. Whereas the seminiferous tubules ofHspa4l −/− 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 inHspa4l −/− 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.