Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Discovery of DYRK1A dependent phosphorylation in mouse embryonic heart

ABSTRACT: The Dp1Tyb mouse model for Down syndrome contains a duplication of 23Mb of mouse chromosome 16 (Mmu16) that is orthologous to human chromosome 21 (Hsa21). This region contains 145 coding genes, and thus these genes are present in 3 copies. Dp1Tyb mice display congenital heart defects, similar to the ones seen in people with Down syndrome. These defects include ventricular and atrio-ventricular septal defects and are seen at embryonic day 14.5 (E14.5) of gestation. One of the 145 genes present in 3 copies in Dp1Tyb mice codes for a kinase called DYRK1A. We found that by crossing Dp1Tyb mice with mice carrying a heterozygous Dyrk1a loss of function allele, thereby reducing the dosage of the Dyrk1a gene from 3 to 2 copies, we rescue the congenital heart defects. Thus 3 copies of Dyrk1a are required to cause heart defects, and, presumably, increased DYRK1A protein is required for the heart defects. We compared the phosphoproteome in Dp1Tyb versus Dp1TybDyrk1a+/+/- embryonic hearts in order to discover alterations in phosphoproteins that could pinpoint molecular mechanisms that give rise to the congenital heart defects. The two strains (Dp1Tyb and Dp1TybDyrk1a+/+/-) differ only in the copy number of Dyrk1a (3 v 2) and thus differences in phosphoproteins would include both direct and indirect targets of DYRK1A activity.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

DISEASE(S): Down Syndrome

SUBMITTER: Helen Flynn

LAB HEAD: Ambrosius P.

PROVIDER: PXD013053 | Pride | 2024-02-01

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	STA7968A12RW10_A1.raw	Raw
	STA7968A12RW11_A1.raw	Raw
	STA7968A12RW13_A1.raw	Raw
	STA7968A12RW22_A1.raw	Raw
	STA7968A12RW23_B1.raw	Raw

Items per page:

1 - 5 of 25

Similar Datasets

Effect of Dyrk1a inhibition on the transcriptome of embryonic hearts from the Dp1Tyb mouse model of Down syndrome using bulk RNAseq

Project description:Embryos from the Dp1Tyb mouse model for Down syndrome (DS) present with congenital heart defects similar to the heart defects seen in humans with DS. We found that genetically reducing the copy number of the Dyrk1a gene (one of the genes in 3 copies in DS) from 3 to 2, normalised some of the transcriptomic changes in Dp1Tyb embryonic hearts and rescued congenital heart defects. Here we treated pregnant mice carrying Dp1Tyb and wild-type (WT) embryos with a Dyrk1a pharmacological inhibitor (Leucettinib-21 or L21) or an inactive isomer (Iso-L21) to study the effect of L21 on the transcriptome of Dp1Tyb and WT embryonic hearts.

2024-01-25 | GSE239798 | GEO

ERBB2 R599C variant is associated with left ventricular outflow tract obstruction defects in human

Project description:Non-syndromic congenital heart defects (CHD) are occasionally familial and left ventricular out flow tract obstruction (LVOTO) defects are among the subtypes with the highest hereditability. The aim of this study was to evaluate the pathogenicity of a heterozygous ERBB2 variant R599C identified in three families with LVOTO defects.

2023-10-19 | MSV000093153 | MassIVE

Molecular Signatures of cardiac defects in Down syndrome lymphoblastoid cell lines (congenital heart disease)

Project description:Molecular Signatures of cardiac defects in Down syndrome lymphoblastoid cell lines. In this study, we want to identify genes and pathways specifically dysregulated in atrioventricular septal defect and /or atrial septal defect + ventricular septal defect in case of trisomy 21. Total RNA obtained from DS lymphoblastoid cell lines without congenital heart disease compared to cell lines from DS with congenital heart disease.

2012-08-14 | E-GEOD-34457 | biostudies-arrayexpress

Whole genome microarray gene expression profiling of right ventricular heart specimens from pediatric patients with Tetralogy of Fallot (TOF)

Project description:Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect with a world-wide prevalence of 3 to 4 cases per 10,000 life births. TOF is a congenital heart disease with four major cardiac defects, i.e., ventricular septal defect, overriding aortic root, infundibular stenosis of the pulmonary artery, and right ventricular hypertrophy. Treatment relies on correction surgery in early infancy. This study performed whole genome microarray gene expression profiling of cardiac specimens of the right ventricular outflow tract (RVOT), which were recovered during correction surgery of TOF from 11 pediatric patients diagnosed with TOF cardiac defects.

2023-09-18 | GSE241024 | GEO

Exome sequencing of Congenital Heart Disease families from the Competence Network Berlin

Project description:This project aims to study exomes from families and trios with congenital heart disease (CHD). The samples have been collected under the Competence Network - Congenital Heart Defects in Berlin, Germany. The phenotypes are mainly left ventricular outflow obstruction (aortic stenosis, bicuspd aortic valve disease coarctation and hypoplastic left heart), but will also include samples with hypoplastic right heart and atrioventricular septal defects. We will perform whole exome sequencing using Agilent sequence capture and Illumina HiSeq sequencing.

| EGAS00001000368 | EGA

EGAS00001000368-sc-20140326 - samples

| EGAD00001000800 | EGA

AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a new mouse model of inherited phosphoglucomutase 1 deficiency (PGM1-CDG)

Project 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.

2023-08-18 | PXD036271 | Pride

Homo sapiens

Project description:Family Genomics of Congenital Heart Defects

| PRJNA252542 | ENA

Homo sapiens

Project description:Family Genomics of Congenital Heart Defects

| PRJNA252541 | ENA

Increased Hemodynamic Load in Early Embryonic Stages Alters Endocardial to Mesenchymal Transition

Project description:Normal blood flow is essential for proper heart formation during embryonic development, as abnormal hemodynamic load (blood pressure and shear stress) results in cardiac defects seen in congenital heart disease. However, the progressive detrimental remodeling processes that relate altered blood flow to cardiac defects remain unclear. Outflow tract banding was used to increase hemodynamic load in the chicken embryo heart between Hamburger and Hamilton stages 18 and 24. Increased hemodynamic load induced increased cell density in outflow tract cushions, fewer cells along the endocardial lining, endocardium junction disruption, and altered periostin expression as measured by confocal microscopy analysis. Proteomic mass-spectrometry analysis quantified altered protein composition after banding.

2019-07-17 | MSV000084103 | MassIVE

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data