Open AccessImpaired fertility in mice deficient for the testicular germ-cell protease PC4
Author(s) -
Majambu Mbikay,
Haidy Tadros,
Norito Ishida,
Charles P. Lerner,
Eve de Lamirande,
A Chen,
Mohamed ElAlfy,
Y. Clermont,
Nabil G. Seidah,
Michel Chrétien,
Claude Gag,
Elizabeth M. Simpson
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.13.6842
Subject(s) - biology , proteases , mutant , germ cell , null allele , spermatogenesis , genetics , microbiology and biotechnology , pronucleus , loss of heterozygosity , allele , embryo , andrology , zygote , embryogenesis , endocrinology , gene , enzyme , biochemistry , medicine
PC4 is a member of the proprotein convertase family of serine proteases implicated in the processing of a variety of polypeptides including prohormones, proneuropeptides, and cell surface proteins. In rodents, PC4 transcripts have been detected in spermatocytes and round spermatids exclusively, suggesting a reproductive function for this enzyme. In an effort to elucidate this function, we have disrupted its locus (Pcsk4) by homologous recombination in embryonic stem cells and have produced mice carrying the mutation. In intercrosses of heterozygous mutant mice, there was low transmission of the mutant Pcsk4 allele to the progeny, resulting in lower than expected incidence of heterozygosity and null homozygosity. The in vivo fertility of homozygous mutant males was severely impaired in the absence of any evident spermatogenic abnormality. In vitro, the fertilizing ability of Pcsk4 null spermatozoa was also found to be significantly reduced. Moreover, eggs fertilized by these spermatozoa failed to grow to the blastocyst stage. These results suggest that PC4 in the male may be important for achieving fertilization and for supporting early embryonic development in mice.