The mature mammalian egg is transcriptionally quiescent, and embryonic transcription is not fully activated until the 2-cell stage (Bevilacqua et al., 1992; Clegg and Piko, 1983). Consequently, oocyte maturation and early mammalian embryogenesis appear to be controlled by timed activation of transcripts expressed in the growing oocyte and stored for later translation (de Moor and Richter, 1999; Oh et al., 1999; Stutz et al., 1998). These maternally derived transcripts are responsible for the completion of meiosis, initiation of mitosis, activation of the embryonic genome, and completion of the transformation of the highly differentiated oocyte into a totipotent embryonic cell. To study the effect of specific maternal transcripts on these processes, we have sought to establish a Cre-loxP conditional knockout system for oocytes.

The zona pellucida (Zp3) gene is specifically expressed in mouse oocytes (Epifano et al., 1995). Using this promoter, it is thus possible to direct Cre expression to the time when maternal genes are transcribed and inactivate targeted genes in the maturing oocyte and embryo. A Zp3-Cre transgenic line, FVB-TgN (Zp3-Cre) 3Mrt, was reported to recombine target genes exclusively in the germ line of hemizygous females (Lewandowski et al., 1997). Unfortunately, homozygous females in this FVB/N lineage are subfertile (3.7 pups/litter), rendering them unsuitable for analyzing the effect of maternal transcripts on embryogenesis. Using a slightly different construct (Fig. 1a), we established seven Zp3-Cre transgenic founders on a C57BL/6J (B6) background [C57BL/6-TgN (Zp3-Cre) Knw]. We analyzed the litters born to females from four lines (Zp3-Cre82, 83, 89, and 93) that reliably transmitted the transgene. Hemizygous transgenic females produced on average six pups/litter, significantly more than the Zp3-Cre3Mrt line (two and one-half pups/litter in the ninth backcross to B6), and indistinguishable from control B6 mice (Fig. 1b). To determine whether Cre recombinase was active in the female germ cells, females homozygous for af loxed β-catenin gene (official gene symbol: CatnbF, referred to as: βF-cat/βF-cat) were mated to males