GATA4 transgenic mice as an in vivo model of congenital heart disease

Han, Hua; Chen, Yu; Liu, Gang; Han, Zengqiang; Zhao, Zhou; Tang, Yin

doi:10.3892/ijmm.2015.2178

Cited by 17 publications

(14 citation statements)

References 30 publications

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“…This mutation impairs GATA4's interaction with another ZF protein FOG2 . Finally, transgenic Gata4 mice with the M310V atrial septal defect (ASD) causing mutation show impairment in GATA4 ability to activate downstream myocardial promoters …”

Section: Congenital Heart Diseases and Gata Mutationsmentioning

confidence: 99%

From embryogenesis to adulthood: Critical role for GATA factors in heart development and function

2019

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Cardiac development is governed by a complex network of transcription factors (TFs) that regulate cell fates in a spatiotemporal manner. Among these, the GATA family of zinc finger TFs plays prominent roles in regulating the development of the myocardium, endocardium, and outflow tract. This family comprises six members three of which, GATA4, 5, and 6, are predominantly expressed in cardiac cells where they activate specific downstream gene targets via interactions with one another and with other TFs and signaling molecules. Their critical function in heart formation is evidenced by the phenotypes of animal models lacking these factors and by the broad spectrum of human congenital heart diseases associated with mutations in their genes. Similarly, in the postnatal heart, these proteins play significant and nonredundant roles in cardiac function, regulating adaptive stress responses including cardiomyocyte hypertrophy and survival, as well as endothelial homeostasis and angiogenesis. As such, decreased expression of either GATA4, 5, or 6 results in impaired cardiovascular homeostasis and increased risk of premature and serious cardiovascular events such as hypertension, arrhythmia, aortopathy, and heart failure. Although a great deal of progress has been made in understanding GATA‐dependent regulatory processes in the heart, the molecular mechanisms underlying the specificity of GATA factors and their upstream regulation remain incompletely understood. The knowledge and tools developed since their discovery 25 years ago should accelerate progress toward further elucidation of their mechanisms of action in health and disease. This in turn will greatly improve diagnosis and care for the millions of individuals affected by congenital and acquired cardiac disease worldwide.

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Section: Congenital Heart Diseases and Gata Mutationsmentioning

confidence: 99%

From embryogenesis to adulthood: Critical role for GATA factors in heart development and function

2019

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“…Several well-established cardiac transcription factors that are highly expressed in cardiogenic plates such as NKX2.5, GATA4, and TBX5 have been extensively studied in both human [47] and animal experiments [48,49]. Mutations in these cardiac transcription factors are associated with most non-syndromic CHDs [50].…”

Section: Introductionmentioning

confidence: 99%

Congenital heart diseases: genetics, non-inherited risk factors, and signaling pathways

Suluba

Liu

Xia

et al. 2020

Egypt J Med Hum Genet

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Background: Congenital heart diseases (CHDs) are the most common congenital anomalies with an estimated prevalence of 8 in 1000 live births. CHDs occur as a result of abnormal embryogenesis of the heart. Congenital heart diseases are associated with significant mortality and morbidity. The damage of the heart is irreversible due to a lack of regeneration potential, and usually, the patients may require surgical intervention. Studying the developmental biology of the heart is essential not only in understanding the mechanisms and pathogenesis of congenital heart diseases but also in providing us with insight towards developing new preventive and treatment methods. Main body: The etiology of congenital heart diseases is still elusive. Both genetic and environmental factors have been implicated to play a role in the pathogenesis of the diseases. Recently, cardiac transcription factors, cardiacspecific genes, and signaling pathways, which are responsible for early cardiac morphogenesis have been extensively studied in both human and animal experiments but leave much to be desired. The discovery of novel genetic methods such as next generation sequencing and chromosomal microarrays have led to further study the genes, non-coding RNAs and subtle chromosomal changes, elucidating their implications to the etiology of congenital heart diseases. Studies have also implicated non-hereditary risk factors such as rubella infection, teratogens, maternal age, diabetes mellitus, and abnormal hemodynamics in causing CHDs. These etiological factors raise questions on multifactorial etiology of CHDs. It is therefore important to endeavor in research based on finding the causes of CHDs. Finding causative factors will enable us to plan intervention strategies and mitigate the consequences associated with CHDs. This review, therefore, puts forward the genetic and non-genetic causes of congenital heart diseases. Besides, it discusses crucial signaling pathways which are involved in early cardiac morphogenesis. Consequently, we aim to consolidate our knowledge on multifactorial causes of CHDs so as to pave a way for further research regarding CHDs. Conclusion: The multifactorial etiology of congenital heart diseases gives us a challenge to explicitly establishing specific causative factors and therefore plan intervention strategies. More well-designed studies and the use of novel genetic technologies could be the way through the discovery of etiological factors implicated in the pathogenesis of congenital heart diseases.

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“…[ 20 ] Han et al explored the role of GATA4 M310 V mutation in CHD development utilizing GATA4 transgenic mice, and the results showed that this polymorphism was significantly correlated with the disease development. [ 21 ] According to the report of Sanchez-Castro et al, the upstream deletions of transcription factor gene SRY-box transcription factor 9 ( SOX9 ) might contribute to the pathogenesis of CHD. [ 22 ]…”

Section: Resultsmentioning

confidence: 99%

Connection of GLI1 variants to congenital heart disease susceptibility

2020

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The purpose of this study was to investigate the relationship between glioma-associated oncogene homolog 1 ( GLI1 ) rs2228226 and rs10783826 polymorphisms and congenital heart disease (CHD) risk in a Chinese Han population. Genotyping for our interested polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism in 106 CHD patients and 112 healthy controls. Hardy–Weinberg equilibrium status in the control group was also checked via χ 2 test. Differences in genotype and allele frequencies between the case and control groups were analyzed adopting Chi-Squared test as well, and the relative risk of CHD resulting from GLI1 genetic variants was checked via calculating odds ratio (OR) and 95% confidence interval (95%CI). CC genotype of rs2228226 showed significantly higher frequency in CHD patients than in controls ( P = .011), indicating that it increased the disease risk (OR = 3.257, 95%CI = 1.280–8.287). Similarly, C allele of the polymorphism elevated CHD incidence by 1.609 folds, compared with G allele (OR = 1.609, 95%CI = 1.089–2.376). However, rs10783826 was not correlated with the occurrence of CHD. GLI1 rs2228226 polymorphism may be a risk factor for CHD in Chinese Han population, but not rs10783826.

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GATA4 transgenic mice as an in vivo model of congenital heart disease

Cited by 17 publications

References 30 publications

From embryogenesis to adulthood: Critical role for GATA factors in heart development and function

From embryogenesis to adulthood: Critical role for GATA factors in heart development and function

Congenital heart diseases: genetics, non-inherited risk factors, and signaling pathways

Connection of GLI1 variants to congenital heart disease susceptibility

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