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Updated: May 31, 2026
Murine Fetal Echocardiography
Published on: February 15, 2013
Embryonic lethality in mice lacking the nuclear factor of activated T cells 5 protein due to impaired cardiac
Man Chi Mak1, Ka Man Lam, Ping Kei Chan
1Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
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.
Insights
Nuclear factor of activated T cells 5 (NFAT5) is crucial for embryonic development, particularly heart formation. NFAT5 knockout mice embryos exhibit cardiac defects and die by E14.5, indicating NFAT5
Area of Science:
- Molecular Biology
- Developmental Biology
- Cardiovascular Science
Background:
- Nuclear factor of activated T cells 5 (NFAT5) regulates genes for osmotic stress adaptation, immune function, myogenesis, and cancer invasion.
- Its precise role in embryonic development, especially cardiac function, remains incompletely understood.
Purpose of the Study:
- To investigate the function of NFAT5 in embryonic development by creating and analyzing NFAT5 gene knockout mice.
Main Methods:
- Generation of homozygous NFAT5 null (NFAT5(-/-)) mice.
- Phenotypic analysis of NFAT5(-/-) embryos, including developmental stage, morphology, and cardiac structure.
- Assessment of cardiomyocyte proliferation, apoptosis, beating rate, and calcium signaling.
- Analysis of gene expression for NFAT5 targets (HSP 70, SMIT) and key cardiac proteins (SERCA, RyR).
Main Results:
- NFAT5(-/-) mouse embryos exhibited developmental failure, dying after E14.5, with observed peripheral edema and abnormal heart development (thin ventricular walls, reduced myocardial cell density).
- NFAT5 deficiency led to reduced cardiomyocyte proliferation (decreased PCNA) and increased apoptosis (increased caspase-3).
- NFAT5(-/-) cardiomyocytes displayed reduced beating rates and aberrant Ca(2+) signaling due to decreased SERCA and RyR expression, along with reduced expression of NFAT5 target genes.
Conclusions:
- NFAT5 plays an essential role in embryonic cardiac development and cardiomyocyte calcium signaling.
- Cardiac failure, resulting from NFAT5 deficiency, is the likely cause of embryonic lethality and observed edema in NFAT5(-/-) embryos.
