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Article: Embryonic lethality in mice lacking the nuclear factor of activated t cells 5 protein due to impaired cardiac development and function

TitleEmbryonic lethality in mice lacking the nuclear factor of activated t cells 5 protein due to impaired cardiac development and function
Authors
Issue Date2011
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2011, v. 6 n. 7 How to Cite?
AbstractNuclear 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. © 2011 Mak et al.
Persistent Identifierhttp://hdl.handle.net/10722/137191
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong7504/06M
Funding Information:

This work was supported by the Research Grant Council Grants The University of Hong Kong 7504/06M. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorMak, MCen_HK
dc.contributor.authorLam, KMen_HK
dc.contributor.authorChan, PKen_HK
dc.contributor.authorLau, YBen_HK
dc.contributor.authorTang, WHen_HK
dc.contributor.authorYeung, PKKen_HK
dc.contributor.authorKo, BCBen_HK
dc.contributor.authorChung, SMSen_HK
dc.contributor.authorChung, SKen_HK
dc.date.accessioned2011-08-26T14:18:29Z-
dc.date.available2011-08-26T14:18:29Z-
dc.date.issued2011en_HK
dc.identifier.citationPlos One, 2011, v. 6 n. 7en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137191-
dc.description.abstractNuclear 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. © 2011 Mak et al.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshCalcium Signaling-
dc.subject.meshCardiovascular Abnormalities - complications - pathology - physiopathology-
dc.subject.meshEmbryo Loss - metabolism - pathology - physiopathology-
dc.subject.meshHeart - embryology - physiopathology-
dc.subject.meshTranscription Factors - deficiency - genetics - metabolism-
dc.titleEmbryonic lethality in mice lacking the nuclear factor of activated t cells 5 protein due to impaired cardiac development and functionen_HK
dc.typeArticleen_HK
dc.identifier.emailChung, SK:skchung@hkucc.hku.hken_HK
dc.identifier.authorityChung, SK=rp00381en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0019186en_HK
dc.identifier.pmid21765887-
dc.identifier.pmcidPMC3134469-
dc.identifier.scopuseid_2-s2.0-79960196928en_HK
dc.identifier.hkuros189421en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79960196928&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.issue7en_HK
dc.identifier.spagee19186en_US
dc.identifier.epagee19186en_US
dc.identifier.eissn1932-6203-
dc.identifier.isiWOS:000292699000001-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridMak, MC=47461427100en_HK
dc.identifier.scopusauthoridLam, KM=47461463900en_HK
dc.identifier.scopusauthoridChan, PK=47461048900en_HK
dc.identifier.scopusauthoridLau, YB=47461442000en_HK
dc.identifier.scopusauthoridTang, WH=24399936100en_HK
dc.identifier.scopusauthoridYeung, PKK=35486097200en_HK
dc.identifier.scopusauthoridKo, BCB=7102833927en_HK
dc.identifier.scopusauthoridChung, SMS=47460923400en_HK
dc.identifier.scopusauthoridChung, SK=7404292976en_HK

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