The acrosomal protein Dickkopf-like 1 (DKKL1) is not essential for fertility.
OBJECTIVE
To determine the role of Dkkl1 on mouse development, viability, and fertility.


METHODS
Prospective experimental study.


METHODS
Government research institution.


METHODS
Mice of C57BL/6 and 129X1/SvJ strains, as well as transgenic mice of mixed C57BL/6 and 129X1/SvJ strains were used for the studies.


METHODS
Mice were constructed that lacked a functional Dkkl1 gene.


METHODS
Deletion of the gene was confirmed by DNA, RNA, and protein analyses; in vivo fertility was examined by continuous mating scheme.


RESULTS
Previous studies have shown that Dkkl1, a gene unique to mammals, is expressed predominantly, if not exclusively, in developing spermatocytes, and the DKKL1 protein accumulates in the acrosome of mature sperm. Subsequent studies (reported in the accompanying article) demonstrate that Dkkl1 also is expressed in the trophectoderm/placental lineage. Taken together, these results strongly suggested that DKKL1 protein is required for terminal differentiation either of trophoblast giant cells or of sperm, both of which are directly involved in fertility. To challenge this hypothesis, conditional targeted mutagenesis was used to ablate the Dkkl1 gene in mice. Surprisingly, Dkkl1 nullizygous embryos developed into viable, fertile adults, despite the fact that they failed to produce any portion of the DKKL1 protein.


CONCLUSIONS
DKKL1 is a mammalian-specific acrosomal protein that is not essential either for development or fertility.
Kaneko
Kotaro J
KJ
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2753, USA.
Kohn
Matthew J
MJ
Liu
Chengyu
C
DePamphilis
Melvin L
ML
D000177:Acrosome / Q000378:metabolism*; D000375:Aging; D000818:Animals; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development; D005260:Female; D005298:Fertility; D018507:Gene Expression Regulation, Developmental; D008098:Litter Size; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C414705:soggy protein, mouse