Targeted disruption of the murine junD gene results in multiple defects in male reproductive function.
JunD is one of three mammalian Jun proteins that contribute to the AP-1 transcription factor complex. Distinct regulation and functions have been proposed for each Jun member, but less is known about the biological functions of each of these proteins in vivo. To investigate the role of JunD, we have inactivated the murine gene by replacement with a bacterial lacZ reporter gene. Embryonic JunD expression was initially detected in the developing heart and cardiovascular system. Subsequent broadening phases of JunD expression were observed during embryonic development and expression in the adult was widespread in many tissues and cell lineages. Mutant animals lack JunD mRNA and protein and showed no evidence of upregulation of c-Jun and JunB mRNA levels. In contrast to the other two Jun members, homozygous JunD-/- mutant animals were viable and appeared healthy. However, homozygous JunD-/- animals showed a reduced postnatal growth. Furthermore, JunD-/- males exhibited multiple age-dependent defects in reproduction, hormone imbalance and impaired spermatogenesis with abnormalities in head and flagellum sperm structures. No defects in fertility were observed in JunD-/- female animals. These results provide evidence for redundant functions for members of the Jun family during development and specific functions for JunD in male reproductive function.
Thépot
D
D
Laboratoire de Biologie Cellulaire et Moléculaire, INRA, Jouy-en-Josas, France.
Weitzman
J B
JB
Barra
J
J
Segretain
D
D
Stinnakre
M G
MG
Babinet
C
C
Yaniv
M
M
D000818:Animals; D002460:Cell Line; D005260:Female; D015870:Gene Expression; D018390:Gene Targeting; D007248:Infertility, Male / Q000235:genetics* / Q000503:physiopathology; D007763:Lac Operon; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D010641:Phenotype; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000502:physiology*; D013091:Spermatogenesis; D013094:Spermatozoa / Q000473:pathology
D016755:Proto-Oncogene Proteins c-jun