Embryonic Lethality in Mice Lacking the Nuclear Factor of Activated T Cells 5 Protein Due to Impaired Cardiac Development and Function

by Man Chi Mak, Ka Man Lam, Ping Kei Chan, Yu Bond Lau, Wai Ho Tang, Patrick Ka Kit Yeung, Ben Chi Bun Ko, Stephen Man Sum Chung, Sookja Kim Chung

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 Ca²⁺ signaling profile as a consequence of reduced sarco(endo)plasmic reticulum Ca²⁺-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 Ca²⁺ signaling. Cardiac failure is most likely responsible for the peripheral edema and death of NFAT5^−/− embryos at E14.5 days.

For the full article visit:
Embryonic Lethality in Mice Lacking the Nuclear Factor of Activated T Cells 5 Protein Due to Impaired Cardiac Development and Function
Syndicated from:PLoS ONE

Article is licensed under a Creative Commons Attribution License.