To identify defects in the embryonic development of BptfXG023 and BptfΔExon2 homozygotes, we performed whole mount examinations of mutant embryos. Growth defects increasing in severity from E5.5 to E7.5 were observed (Figure 1A) (Figure S5A). Dissections conducted at E8.5 and E9.5 were uninformative, because a majority of the embryos had been completely reabsorbed (data not shown). We crossed BptfXG023 and BptfΔExon2 heterozygous mice to generate the trans-heterozygous BptfXG023/BptfΔExon2 embryos. The trans-heterozygote recapitulated the growth defects of the BptfXG023 and BptfΔExon2 homozygotes, indicating that the two mutations are functionally equivalent (Figure S5B). To determine whether the developmental defects originated before implantation, we harvested E3.5 blastocysts and performed blastocyst outgrowth assays. We observed normal E3.5 homozygous BptfXG023 and BptfΔExon2 blastocysts and normal outgrowths from the blastocysts after tissue culture for 5 days, suggesting that either Bptf is not essential for pre-implantation development or that the maternal Bptf protein or mRNA can mask pre-implantation phenotypes (Figure S6). The masking of pre-implantation phenotypes by maternal Bptf is possible because it is highly expressed in oocytes [27],[28].
