GEO series

Genetically Engineered Mouse Models Unveil Mechanisms and Therapeutic Strategies for GMPPB-Associated Dystroglycanopathy I

GSE268448 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/05/17 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 12 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 12 samples: 12 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.

Summary (written by the submitters)

Recent studies have highlighted a significant association between mutations in GDP-mannose pyrophosphorylase B (GMPPB) gene with dystroglycanopathy (DGP), a rare disease characterized by neuromuscular phenotypes. To interrogate the molecular mechanisms driving the onset and progression and to identify potential therapeutic approaches for GMPPB-associated DGP, we here constructed genetically engineered mice models of Gmppb.

Read the full summary ↓

We show that Gmppb knockout and P32L mutant mice are lethal in the homozygous form, whereas homologous R287Q mutants are viable. Heterozygous Gmppb-P32L mutant mice exhibit reduced muscle strength, decreased locomotor ability, elevated creatine kinase levels and increased centrally nucleated myofibers. Furthermore, loss of GMPPB results in defective differentiation of muscle stem cells, leading to failure to develop into mature myotubes and diminished muscle regeneration capability. Biochemical and transcriptomic analyses indicate that loss of GMPPB is associated with significant alterations in O-linked glycosylation level, intracellular Ca2+ storage and release and the Wnt/β-catenin signaling pathway. Pharmacological activation of the Wnt pathway alleviated disruption of muscle differentiation and regeneration post muscle injury in Gmppb-deficient models. Additionally, adeno-associated virus (AAV)-mediated gene replacement therapy successfully ameliorated the muscular phenotypes. Collectively, our findings provide direct evidence that impaired muscle stem cell differentiation contributes to GMPPB-associated dystroglycanopathy. Wnt pathway agonists and AAV gene therapy represent potential effective intervention strategies for treating DGP disease.

This dataset

Open GSE268448 in finder → Find more mouse RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE268448_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1117393 and SRA study SRP510244. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41957353) ↗

Study design

12 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 12 sample titles: 12 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8291481 wild-type mice_1, 32-week-old
GSM8291482 wild-type mice_2, 32-week-old
GSM8291483 wild-type mice_3, 32-week-old
GSM8291484 Gmppb-KO mice_1, 32-week-old
GSM8291485 Gmppb-KO mice_2, 32-week-old
GSM8291486 Gmppb-KO mice_3, 32-week-old
GSM8291487 Gmppb-P32L mice_1, 32-week-old
GSM8291488 Gmppb-P32L mice_2, 32-week-old
GSM8291489 Gmppb-P32L mice_3, 32-week-old
GSM8291490 Gmppb-R287Q mice_1, 32-week-old
GSM8291491 Gmppb-R287Q mice_2, 32-week-old
GSM8291492 Gmppb-R287Q mice_3, 32-week-old

Datasets on a similar topic

GSE296090 Combinatorial Immunotherapeutic Strategies in Liver Cancer 18 samples shares therapeutic, strategies
GSE294832 Modular neuroinflammatory network discovery from large-scale phenotypic screening in genetically heterogeneous mice [part10] 1000 samples shares genetically
GSE294911 Modular neuroinflammatory network discovery from large-scale phenotypic screening in genetically heterogeneous mice [part14] 1000 samples shares genetically
GSE294535 Modular neuroinflammatory network discovery from large-scale phenotypic screening in genetically heterogeneous mice[part5] 1000 samples shares genetically
GSE294849 Modular neuroinflammatory network discovery from large-scale phenotypic screening in genetically heterogeneous mice [part13] 1000 samples shares genetically
GSE294826 Modular neuroinflammatory network discovery from large-scale phenotypic screening in genetically heterogeneous mice [part9] 1000 samples shares genetically
GSE294983 Modular neuroinflammatory network discovery from large-scale phenotypic screening in genetically heterogeneous mice [part20] 1000 samples shares genetically
GSE294958 Modular neuroinflammatory network discovery from large-scale phenotypic screening in genetically heterogeneous mice [part17] 1000 samples shares genetically

Search all mouse RNA-seq datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.