Overexpression of Jazf1 induces cardiac malformation through the upregulation of pro-apoptotic genes in mice

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Title
Overexpression of Jazf1 induces cardiac malformation through the upregulation of pro-apoptotic genes in mice
Author(s)
K B Bae; M O Kim; D H Yu; M J Shin; H J Kim; H S Yuh; Y R Ji; J Y Kim; J M Kim; Byung Hwa Hyun; H C Lee; W K Chang; S B Park; D H Kim; H S Lee; Y S Choo; S Lee; Z Y Ryoo
Bibliographic Citation
Transgenic Research, vol. 20, no. 5, pp. 1019-1031
Publication Year
2011
Abstract
The transcription factor Juxtaposed with another zinc finger gene 1 (JAZF1) is a zinc finger protein that binds to the nuclear orphan receptor TR4. Recent evidence indicates that TR4 receptor functions as both a positive and negative regulator of transcription, but the role of JAZF1 in transcriptional mechanisms has not been elucidated. Recently, the incidence rate of congenital heart malformations was reported to be significantly elevated in patients who had neurofibromatosis 1 (NF1) with chromosomal microdeletion syndrome. Furthermore, Joined to JAZF1 (SUZ12) is expressed at high levels in the hearts of adult patients with NF1 microdeletion syndrome. Therefore, we hypothesized that ectopic expression of JAZF1 may lead to cardiac malformations that deleteriously affect the survival of neonates and adults. We sought to elucidate the role of JAZF1 in cardiac development using a Jazf1-overexpressing (Jazf1-Tg) mouse model. In Jazf1-Tg mice, Jazf1 mRNA expression was significantly elevated in the heart. Jazf1-Tg mice also showed cardiac defects, such as high blood pressure, electrocardiogram abnormalities, apoptosis of cardiomyocytes, ventricular non-compaction, and mitochondrial defects. In addition, we found that the expression levels of pro-apoptotic genes were elevated in the hearts of Jazf1-Tg mice. These findings suggest that Jazf1 overexpression may induce heart failure symptoms through the upregulation of pro-apoptotic genes in cardiomyocytes.
Keyword
ApoptosisCardiac developmentJazf1Transgenic mice
ISSN
0962-8819
Publisher
Springer
DOI
http://dx.doi.org/10.1007/s11248-010-9476-4
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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