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

Ki Beom Bae, Myoung Ok Kim, Dong Hoon Yu, Mi Jung Shin, Hei Jung Kim, Hyung Soo Yuh, Young Rae Ji, Jae Young Kim, Jin Man Kim, Byung Hwa Hyun, Hwi Cheul Lee, Won Kyong Chang, Soo Bong Park, Do Hyung Kim, Hyun Shik Lee, Yeon Sik Choo, Sanggyu Lee, Zae Young Ryoo

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1019-1031
Number of pages13
JournalTransgenic Research
Volume20
Issue number5
DOIs
StatePublished - Oct 2011

Bibliographical note

Funding Information:
Acknowledgments This research was supported by the SRC program (Center for Food & Nutritional Genomics: grant number 2010-0001886) of the National Research Foundation (NRF) of Korea funded by the Ministry of Education, Science and Technology, a grant from the BioGreen 21 Program (no. PJ0071812009), Rural Development Administration, Republic of Korea, and the Grant of the Korean Ministry of Education, Science and Technology (The Regional Core Research Program/Anti-aging and Well-being Research Center).

Keywords

  • Apoptosis
  • Cardiac development
  • Jazf1
  • Transgenic mice

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