title: Adult onset cardiac dilatation in a transgenic mouse line with Galβ1,3GalNAc α2,3-sialyltransferase II (ST3Gal-II) transgenes: a new model for dilated cardiomyopathy.
abstract: Sugar chain abnormalities in glycolipids and glycoproteins are associated with various diseases. Here, we report an adult onset cardiac dilatation in a transgenic mouse line with Galβ1,3GalNAc α2,3-sialyltransferase II (ST3Gal-II) transgenes. The transgenic hearts at the end-stage, at around 7 months old, were enlarged, with enlarged cavities and thin, low-tensile walls, typical of dilated cardiomyopathy. Although no apparent change was found in heart gangliosides, glycosylation of heart proteins was altered. Interestingly, sugar moieties not directly related to the ST3Gal-II catalytic reaction were also changed. Significant increases in calreticulin and calnexin were observed in hearts of the transgenic mice. These results suggest that expression of ST3Gal-II transgenes induces abnormal protein glycosylation, which disorganizes the endoplasmic/sarcoplasmic reticulum quality control system and elevates the calreticulin/calnexin level, resulting in suppression of cardiac function. The transgenic mice showed 100% incidence of adult onset cardiac dilatation, suggesting great potential as a new model for dilated cardiomyopathy.
authors: Laboratory of Animal Models for Human Diseases, National Institute of Biomedical Innovation, Ibaraki, Japan. osuzuki@nibio.go.jp
authors: Osamu
authors: O
authors: Suzuki
authors: Takao
authors: T
authors: Kanai
authors: Toshio
authors: T
authors: Nishikawa
authors: Yoshie
authors: Y
authors: Yamamoto
authors: Akira
authors: A
authors: Noguchi
authors: Kazuhiro
authors: K
authors: Takimoto
authors: Minako
authors: M
authors: Koura
authors: Yoko
authors: Y
authors: Noguchi
authors: Kozue
authors: K
authors: Uchio-Yamada
authors: Shuichi
authors: S
authors: Tsuji
authors: Junichiro
authors: J
authors: Matsuda
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D037281:Calnexin / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000201:enzymology* / Q000473:pathology*; D004195:Disease Models, Animal; D005629:Frozen Sections; D005732:Gangliosides / Q000378:metabolism; D006720:Homozygote; D037102:Lectins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D012799:Sialyltransferases / Q000378:metabolism*; D013194:Staining and Labeling; D019076:Transgenes / Q000235:genetics*; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
chemical_list: D037282:Calreticulin; D005732:Gangliosides; D037102:Lectins; D037281:Calnexin; D012799:Sialyltransferases; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase