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Series GSE134121 Query DataSets for GSE134121
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
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.
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.
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
Organization name Johns Hopkins School of Medicine
Department Department of Medicine
Street address Rangos 471, 855 N. Wolfe Street
City Baltimore
State/province MD
ZIP/Postal code 21205
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (24)
GSM3937545 2086-1_heart_OGA_TG
GSM3937546 2086-2_heart_OGA_TG
GSM3937547 2086-4_heart_OGA_TG
BioProject PRJNA553816
SRA SRP214154

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE134121_Heart_FPKM_matrice.xlsx 4.1 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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