Neonatal Death and Heart Failure in Mouse with Transgenic HSP60 Expression.
Mitochondrial heat shock proteins, such as HSP60, are chaperones responsible for the folding, transport, and quality control of mitochondrial matrix proteins and are essential for maintaining life. Both prosurvival and proapoptotic roles have been proposed for HSP60, and HSP60 is reportedly involved in the initiation of autoimmune, metabolic, and cardiovascular diseases. The role of HSP60 in pathogenesis of these diseases remains unclear, partly because of the lack of mouse models expressing HSP60. In this study we generated HSP60 conditional transgenic mice suitable for investigating in vivo outcomes by expressing HSP60 at the targeted organ in disease models. Ubiquitous HSP60 induction in the embryonic stage caused neonatal death in mice at postnatal day 1. A high incidence of atrial septal defects was observed in HSP60-expressing mice, with increased apoptosis and myocyte degeneration that possibly contributed to massive hemorrhage and sponge-like cardiac muscles. Our results showed that neonatal heart failure through HSP60 induction likely involves developmental defects and excessive apoptosis. The conditional HSP60 mouse model is useful for studying crucial biological questions concerning HSP60.
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
Tsung-Hsien
TH
Chen
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan ; Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
Shan-Wen
SW
Liu
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
Mei-Ru
MR
Chen
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
Kuan-Hung
KH
Cho
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
Tzu-Yin
TY
Chen
Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taipei, Taiwan.
Pao-Hsien
PH
Chu
Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
Yu-Ying
YY
Kao
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
Ching-Han
CH
Hsu
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
Kurt Ming-Chao
KM
Lin
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics; D018834:Chaperonin 60 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006333:Heart Failure / Q000151:congenital / Q000209:etiology* / Q000235:genetics; D006344:Heart Septal Defects, Atrial / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D015854:Up-Regulation
D018834:Chaperonin 60; C557066:Hspd1 protein, mouse; D024101:Mitochondrial Proteins