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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 10, 2021 |
| Title |
Excessive O-GlcNAcylation causes heart failure and sudden death |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Heart failure is a leading cause of death worldwide, and failing heart muscle is marked by increased O-GlcNAcylation (OGN). It is unknown if excessive OGN contributes to cardiomyopathy and heart failure. OGN modifies serines and threonines, total OGN levels follow cellular nutrient and metabolic flux in addition to net activity of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). We developed new transgenic mouse models with myocardial delimited over-expression of OGA and OGT, and found that OGT transgenic mice developed severe cardiomyopathy and premature death. In contrast, OGA transgenic hearts had normal function, but were resistant to pathological stress. Interbreeding OGA transgenic mice rescued cardiomyopathy and premature death in OGT transgenic mice. RNA Seq and functional studies highlighted disrupted metabolism in hearts from OGT transgenic mice that was rescued by OGA transgenic interbreeding. Here we show excessive OGN causes cardiomyopathy, identify gene programs responsive to pathological OGN, and suggest attenuation of OGN may be an effective therapy for heart failure.
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| Overall design |
This poly(A+) transcriptome profiling study examined the cardiac transcriptional profiles of adult wildtype, transgenic OGA and OGT mice, and OGA x OGT double transgenic mice.
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| Contributor(s) |
Umapathi P, Banerjee PS, Zachara NE, Abrol N, Wang Q, Mesubi OO, Luczak ED, Wu Y, Granger JM, Florea L, Talbot C, Hart GW, Anderson ME |
| Citation(s) |
33593071 |
| Submission date |
Jul 10, 2019 |
| Last update date |
Oct 09, 2021 |
| Contact name |
Mark E Anderson |
| E-mail(s) |
mark.anderson@jhmi.edu
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| Organization name |
Johns Hopkins School of Medicine
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| Department |
Department of Medicine
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| Street address |
Rangos 471, 855 N. Wolfe Street
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| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21205 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA553816 |
| SRA |
SRP214154 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE134121_Heart_FPKM_matrice.xlsx |
4.1 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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