 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Apr 14, 2020 |
| Title |
RNA-deep sequencing (RNA-Seq) analysis of dy2J/dy2J (Lama2-CMD mouse model), mdx (DMD mouse model) and Wild-type skeletal muscles |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
|
| |
|
| Overall design |
Quadriceps muscle biopsies from male Wild-type (n=14), dy2J/dy2J (n=11) and mdx (n=15) mice were recruiting at the age of 8 weeks to the experiment in order to analyzed differences in the transcriptome content. Biopsies were taken from each mouse for RNA isolation and subjected for RNA-Seq evaluation. The RNA from WT or mdx genotype was pooled into three batches, 4-6 RNA samples in each pool. Samples from dy2J mice were divided into two batches, 5-6 samples per pool.
|
| |
|
| Contributor(s) |
Yanay N, Nevo Y, Elbaz M, Elgavish S, Nevo Y |
| Citation(s) |
31348492 |
| |
| Submission date |
Feb 11, 2019 |
| Last update date |
Apr 14, 2020 |
| Contact name |
Nurit Yanay |
| E-mail(s) |
nurit.yanay@mail.huji.ac.il
|
| Organization name |
Schneider Children's Medical Center of Israel
|
| Department |
The Institute of Neurology
|
| Lab |
Pediatric Neuromuscular Laboratory
|
| Street address |
Kaplan 14 St.
|
| City |
Petah Tikva |
| ZIP/Postal code |
4920235 |
| Country |
Israel |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (8)
|
|
| Relations |
| BioProject |
PRJNA521797 |
| SRA |
SRP185591 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE126416_gene_exp.xls.gz |
10.0 Mb |
(ftp)(http) |
XLS |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...