Adult onset cardiac dilatation in a transgenic mouse line with Galß1,3GalNAc α2,3-sialyltransferase II (ST3Gal-II) transgenes: a new model for dilated cardiomyopathy.
Proc Jpn Acad Ser B Phys Biol Sci
; 87(8): 550-62, 2011.
Article
in En
| MEDLINE
| ID: mdl-21986317
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 Galß1,3GalNAc 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sialyltransferases
/
Aging
/
Cardiomyopathy, Dilated
/
Transgenes
Limits:
Animals
Language:
En
Journal:
Proc Jpn Acad Ser B Phys Biol Sci
Journal subject:
BIOLOGIA
/
FISIOLOGIA
Year:
2011
Document type:
Article
Affiliation country:
Japan
Country of publication:
Japan