title: Overexpression of Jazf1 induces cardiac malformation through the upregulation of pro-apoptotic genes in mice.
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.
authors.affiliation: School of Life Science and Biotechnology, College of Natural Sciences, Food and Nutritional Genomics Research Center, Kyungpook National University, 1370 Sankyuk-dong, Buk-gu, Daegu 702-701, Korea.
authors.forename: Ki Beom
authors.initials: KB
authors.lastname: Bae
authors.forename: Myoung Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Yu
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Shin
authors.forename: Hei Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hyung Soo
authors.initials: HS
authors.lastname: Yuh
authors.forename: Young Rae
authors.initials: YR
authors.lastname: Ji
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Jin Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Byung Hwa
authors.initials: BH
authors.lastname: Hyun
authors.forename: Hwi Cheul
authors.initials: HC
authors.lastname: Lee
authors.forename: Won Kyong
authors.initials: WK
authors.lastname: Chang
authors.forename: Soo Bong
authors.initials: SB
authors.lastname: Park
authors.forename: Do Hyung
authors.initials: DH
authors.lastname: Kim
authors.forename: Hyun-Shik
authors.initials: HS
authors.lastname: Lee
authors.forename: Yeon-Sik
authors.initials: YS
authors.lastname: Choo
authors.forename: Sanggyu
authors.initials: S
authors.lastname: Lee
authors.forename: Zae Young
authors.initials: ZY
authors.lastname: Ryoo
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D001794:Blood Pressure; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D004562:Electrocardiography; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology / Q000254:growth & development; D006330:Heart Defects, Congenital / Q000235:genetics*; D006333:Heart Failure / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C558308:JAZF1 protein, mouse; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C494163:Suz12 protein, mouse; D063151:Polycomb Repressive Complex 2