Embryonic lethality in mice lacking the nuclear factor of activated T cells 5 protein due to impaired cardiac development and function
Date
2011
Authors
Mak, M. C.
Lam, K. M.
Chan, P. K.
Lau, Y. B.
Tang, W. H.
Yeung, P. K.
Ko, B. C.
Chung, S. M.
Chung, S. K.
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Abstract
Nuclear factor of activated T cells 5 protein (NFAT5) is thought to be important for
cellular adaptation to osmotic stress by regulating the transcription of genes
responsible for the synthesis or transport of organic osmolytes. It is also thought to
play a role in immune function, myogenesis and cancer invasion. To better understand the
function of NFAT5, we developed NFAT5 gene knockout mice. Homozygous NFAT5 null
(NFAT5(-/-)) mouse embryos failed to develop normally and died after 14.5 days of
embryonic development (E14.5). The embryos showed peripheral edema, and abnormal heart
development as indicated by thinner ventricular wall and reduced cell density at the
compact and trabecular areas of myocardium. This is associated with reduced level of
proliferating cell nuclear antigen and increased caspase-3 in these tissues.
Cardiomyocytes from E14.5 NFAT5(-/-) embryos showed a significant reduction of beating
rate and abnormal Ca(2+) signaling profile as a consequence of reduced
sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) and ryanodine receptor (RyR)
expressions. Expression of NFAT5 target genes, such as HSP 70 and SMIT were reduced in
NFAT5(-/-) cardiomyocytes. Our findings demonstrated an essential role of NFAT5 in
cardiac development and Ca(2+) signaling. Cardiac failure is most likely responsible for
the peripheral edema and death of NFAT5(-/-) embryos at E14.5 days.
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Citation
Mak, M. C., K. M. Lam, P. K. Chan, Y. B. Lau, et al. 2011. "Embryonic lethality in mice lacking the nuclear factor of activated T cells 5 protein
due to impaired cardiac development and function." PloS one 6(7): 19186. doi:10.1371/journal.pone.0019186