These defects are partially masked by the early lethality observed in the commercial Tek-Cre mouse line; according to our data all animals carrying homozygous Tek transgene die early in development, providing a 'background' lethality rate of approximately 25%.
With a lethality rate of approximately 60% in reported laboratory-confirmed human H5N1 cases (10), maximum preparedness is warranted in case sustained human-to-human transmission were to evolve.
Injection of 25 pg of full length Mef2ca 4–5–6 RNA had dramatic effects on embryonic development, inducing lethality in approximately 30% of the embryos and marked developmental defects in 49% of the surviving embryos, classified as 'severely defective' (Fig. S6A,B).
Similarly to BE × BE, crosses between two BE2 individuals yielded embryonic lethality in approximately one fourth of the progeny (22.9% of 1488 progeny in eight families) and enlarged eyespots in two thirds of the adults (64.8% of 429 adult offspring).
This was confirmed by complementation tests: crosses between BE and either Fr or Spr mutants yielded embryonic lethality in approximately one fourth of the offspring (23.9% of 4645 progeny in 33 families), with identical morphological aberrations as those found in the offspring of crosses between mutants of the same phenotype.
Embryos were isolated ≥48 hours later at E11.5 and genotyping revealed approximately 50% lethality of the Bmp4Δ/Δc, TMCretg/+ embryos.
Whereas mouse lines that are heterozygous for these insertions show no phenotype, both homozygous lines display heart defects and neural crest defects, resulting in embryonic lethality at approximately 12.5-14 days of gestation (Brannan et al., 1994; Jacks et al., 1994; Lakkis et al., 1999).
SNPs in this category may exhibit strong heterosis, recessive lethality, or be linked with such sites, explaining their persistence at a frequency of approximately 50%.
Mutations that cause a complete block of erythropoiesis, such as loss of erythropoietin or its receptor, lead to embryonic lethality at approximately E13 (Wu et al., 1995).
Indeed, of 40 live born pups examined, only 2 were transgenic (5%), while the transgenic rate of embryonic day 13.5 embryos was approximately 20%, suggesting a partial embryonic lethality of transgenic embryos.
