Unexpected features in mice
with mutant cytochrome c
S.A. Nedospasov
Belozersky Institute of Physico-Chemical Biology and Faculty of Biology, Moscow State
University; Engelhardt Institute of Molecular Biology, Moscow
Cytochrome c released from mitochondria is critical for apoptosome-dependent pathway
of the programmed cell death. Because of its critical involvement also in electron transport,
mice lacking this gene and gene product die at embryonic stage. Certain mutations in cytochrome
c, including K72 position, may dissociate electron transfer functions of this protein from proapoptotic
one (e.g., in the K72W mutant, the latter is inhibited while the former remains intact). Using Cre-LoxP
and Flp/Frt technologies, we have engineered mice with K72W mutation introduced into the germline
in a conditional fashion. In particular, we have generated mice with homozygous K72W mutation in
all cells. Although fraction of these mice displays anatomical abnormalities and die early, some mice
are grossly normal and can live up to 1.5 years. Cells isolated from these mice show partial deficiency
in apoptotic responses in vitro. In vivo studies demonstrated some inhibition of response
of organism to bacterial lipopolysaccharide. Moreover, abnormalities certain in brain/behavioral functions,
were revealed. Overall, this study revealed both expected and unexpected consequences of cytochrome c mutation.
Homo Sapiens Liberatus Workshop, Moscow State University, May 2010