Transcriptomics

Dataset Information

0

RNA-deep sequencing (RNA-Seq) analysis of dy2J/dy2J (Lama2-CMD mouse model), mdx (DMD mouse model) and Wild-type skeletal muscles


ABSTRACT: Congenital muscular dystrophy type-1A (Lama2-CMD) and Duchenne Muscular dystrophy (DMD) result from deficiencies of laminin-α2 and dystrophin proteins, respectively. Although both proteins strengthen the sarcolemma, they are implicated in clinically distinct phenotypes. We used RNA-deep sequencing (RNA-Seq) of dy2J/dy2J, Lama2-CMD mouse model, skeletal muscle at 8 weeks of age to elucidate disease pathophysiology. This study is the first report of dy2J/dy2J model whole transcriptome profile. RNA-Seq of the mdx mouse model of DMD and WT mouse was carried as well in order to enable a novel comparison of dy2J/dy2J to mdx. A large group of shared differentially expressed genes (DEG) were found in dy2J/dy2J and mdx models (1,834 common DEG, (FDR) < 0.05). Enrichment pathway analysis using Ingenuity Pathway Analysis (IPA) showed enrichment of inflammation, fibrosis, cellular movement, migration and proliferation of cells, apoptosis and necrosis in both mouse models (p-values 3E-10 – 9E-37). Via Canonical pathway analysis; Actin cytoskeleton, Integrin, ILK, NF-kB, Renin-angiotensin, calcium signaling were also enriched and upregulated in both models (FDR<0.05). Interestingly, significant downregulation of Pax7 was detected in dy2J/dy2J compared to upregulation of this key regeneration gene in mdx mice. Pax3 and Mamstr genes were also downregulated in dy2J/dy2J compared to WT mice. These results may explain the distinct disease course and severity in these models. While the mdx model at that stage shows massive regeneration, the dy2J/dy2J shows progressive dystrophic process. Our data deepen our understanding of the molecular pathophysiology and suggest new targets for additional therapies to upregulate regeneration in Lama2-CMD.

ORGANISM(S): Mus musculus

PROVIDER: GSE126416 | GEO | 2020/04/14

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2024-09-23 | GSE253680 | GEO
2024-09-02 | BIOMD0000001015 | BioModels
2023-06-16 | GSE225766 | GEO
2016-07-24 | E-GEOD-77126 | biostudies-arrayexpress
2018-10-22 | PXD009680 | Pride
2016-07-24 | GSE77126 | GEO
2010-07-31 | E-GEOD-16438 | biostudies-arrayexpress
2015-09-24 | E-GEOD-64419 | biostudies-arrayexpress
2015-09-24 | E-GEOD-64418 | biostudies-arrayexpress
2021-12-01 | PXD027772 | Pride