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

• Published in: Transgenic research Vol. 20; no. 5; pp. 1019 - 1031
• Main Authors: Bae, Ki Beom, Kim, Myoung Ok, Yu, Dong Hoon, Shin, Mi Jung, Kim, Hei Jung, Yuh, Hyung Soo, Ji, Young Rae, Kim, Jae-Young, Kim, Jin Man, Hyun, Byung Hwa, Lee, Hwi Cheul, Chang, Won Kyong, Park, Soo Bong, Kim, Do Hyung, Lee, Hyun-Shik, Choo, Yeon-Sik, Lee, Sanggyu, Ryoo, Zae Young
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer-Verlag 01-10-2011; Springer Netherlands; Springer; Springer Nature B.V
• Subjects: abnormal development; adults; Animal Genetics and Genomics; Animal models; Animals; Apoptosis; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biotechnology; Blood Pressure; cardiomyocytes; Carrier Proteins - genetics; Carrier Proteins - metabolism; Congenital defects; Disease Models, Animal; EKG; Electrocardiography; Fundamental and applied biological sciences. Psychology; Gene expression; gene expression regulation; Gene Expression Regulation, Developmental; gene overexpression; genes; Genetic Engineering; Genetic technics; Heart; Heart - embryology; Heart - growth & development; Heart Defects, Congenital - genetics; Heart diseases; heart failure; Heart Failure - genetics; Heart rate; Hypertension; Life Sciences; messenger RNA; Methods. Procedures. Technologies; Mice; Mice, Transgenic; Mitochondria; Molecular Medicine; Neonates; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Original Paper; Orphan receptors; patients; Plant Genetics and Genomics; Polycomb Repressive Complex 2; Recklinghausen's disease; Repressor Proteins - genetics; Repressor Proteins - metabolism; RNA, Messenger - metabolism; Survival; Transcription factors; Transgenic animals and transgenic plants; Transgenic mice; Transgenics; zinc finger motif; Zinc finger proteins; Cardiac development; Jazf1; Transgenic mice; Apoptosis; Heart; Vertebrata; Mammalia; Gene; Mouse; Rodentia; Transgenic animal; Gene overexpression
• ISSN: 0962-8819; 1573-9368
• DOI: 10.1007/s11248-010-9476-4

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.