PXD036271 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a new mouse model of inherited phosphoglucomutase 1 deficiency (PGM1-CDG) |
Description | PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is an early onset of dilated cardiomyopathy (DCM). Recently, we discovered that oral D-galactose supplementation improved liver disease, endocrine and coagulation abnormalities, but does not alleviate the fatal cardiomyopathy and the associated myopathy. To study the pathobiology of the cardiac disease observed in PGM1-CDG, we constructed a novel cardiomyocyte-specific conditional Pgm2 (mouse ortholog of human PGM1) knockout (Pgm2 cKO) mouse model. Echocardiography studies corroborated a DCM phenotype with significantly reduced ejection fraction and left ventricular dilatation similar to those seen in individuals with PGM1-CDG. Histological studies demonstrated excess glycogen accumulation and fibrosis, while ultrastructural analysis revealed Z-disk disarray and swollen/fragmented mitochondria. We observed similar ultrastructural pathology in the cardiac explant of an individual with PGM1-CDG. We found decreased mitochondrial function in the heart of Pgm2 cKO mice. Transcriptomic analysis of hearts from Pgm2 cKO mice demonstrated a gene signature of DCM. Although proteomics revealed only mild changes in global protein expression in left ventricular tissue of Pgm2 cKO mice, a glycoproteomic analysis revealed an overall decreased protein glycosylation with significant glycosylation defects in sarcolemmal proteins including different subunits of laminin protein. Finally, augmentation of PGM1 in KO mice via AAV9-PGM1 gene replacement therapy prevented and halted the progression of the DCM phenotype. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_09:04:40.979.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Akhilesh Pandey |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Eclipse |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-08-25 13:32:37 | ID requested | |
1 | 2023-08-18 09:02:43 | announced | |
⏵ 2 | 2023-11-14 09:04:48 | announced | 2023-11-14: Updated project metadata. |
Publication List
Balakrishnan B, Altassan R, Budhraja R, Liou W, Lupo A, Bryant S, Mankouski A, Radenkovic S, Preston GJ, Pandey A, Boudina S, Kozicz T, Morava E, Lai K, AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a mouse model of phosphoglucomutase 1 deficiency (PGM1-CDG). Transl Res, 257():1-14(2023) [pubmed] |
Keyword List
submitter keyword: PGM1-CDG, heart, glycoproteomics, Mouse, Proteomics |
Contact List
Akhilesh Pandey |
contact affiliation | Department of Laboratory Medicine and Pathology Mayo Clinic, Rochester, Minnesota 55905 United States |
contact email | pandey.akhilesh@mayo.edu |
lab head | |
Akhilesh Pandey |
contact affiliation | Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905 |
contact email | pandey.akhilesh@mayo.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD036271 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD036271
- Label: PRIDE project
- Name: AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a new mouse model of inherited phosphoglucomutase 1 deficiency (PGM1-CDG)