Davis AC, Wims M, Spotts GD, Hann SR, Bradley A:
A null c-myc mutation causes lethality before 10.5 days of gestation
in homozygotes and reduced fertility in heterozygous female mice.
Genes & Development 1993 Apr;7(4):671-82
ABSTRACT
To directly assess c-myc function in cellular proliferation,
differentiation, and embryogenesis, we have used homologous
recombination in embryonic stem cells to generate both heterozygous
and homozygous c-myc mutant ES cell lines. The mutation is a null
allele at the protein level. Mouse chimeras from seven heterozygous
cell lines transmitted the mutant allele to their offspring. The
analysis of embryos from two clones has shown that the mutation is
lethal in homozygotes between 9.5 and 10.5 days of gestation. The
embryos are generally smaller and retarded in development compared
with their littermates. Pathologic abnormalities include the heart,
pericardium, neural tube, and delay or failure in turning of the
embryo. Heterozygous females have reduced fertility owing to
embryonic resorption before 9.5 days of gestation in 14% of
implanted embryos. c-Myc protein is necessary for embryonic survival
beyond 10.5 days of gestation; however, it appears to be dispensable
for cell division both in ES cell lines and in the embryo before
that time.
