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Viral-mediated knockdown of Atxn2 attenuates TDP-43 pathology and muscle dysfunction in the PFN1C71G ALS mouse model

GSE297399 Mus musculus (mouse) RNA-seq (gene expression) 52 samples Submitted 2025/05/17 Platform GPL34328
At a glance

RNA-seq (gene expression) · mouse · 52 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
52 samples: 9 conditions, mostly with about 6 replicates eachGroups 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.
Paper
Viral-mediated knockdown of Atxn2 attenuates TDP-43 pathology and muscle dysfunction in the PFN1(C71G) ALS mouse modelActa neuropathologica communications · 2025
Summary (written by the submitters)
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron loss and muscle atrophy. Hyperphosphorylated aggregation of the RNA-binding protein, TDP-43, in the motor cortex and spinal cord are defining molecular features of ALS, suggesting TDP-43 dysfunction underlies disease pathogenesis.
Read the full summary ↓
This phenomenon, however, has been difficult to recapitulate endogenously in animal models, impeding characterization of TDP-43 pathobiology in neurodegeneration. In this study, we report age-dependent accumulation of TDP-43 pathology in the spinal cord and progressive muscle-related deficits in transgenic mice expressing the ALS-associated PFN1C71G mutant protein. We show that transgenic neuronal expression of PFN1C71G induces early hyperphosphorylation of endogenous TDP-43 in the spinal cord that augments over time, preceding accumulation of insoluble non-phosphorylated TDP-43 and the manifestation of muscle denervation and motor dysfunction. Sustained knockdown of Atxn2 in the central nervous system (CNS) in pre-symptomatic PFN1C71G mice by AAV-driven expression of an artificial microRNA (AAV-amiR-Atxn2) reduces aberrant TDP-43 in the spinal cord, while delaying neurodegeneration and improving muscle and motor function. RNA-sequencing analysis of spinal cord samples from PFN1C71G mice and ALS donors show shared patterns of transcriptional perturbation, including a pro-inflammatory gene signature that is attenuated by AAV-amiR-Atxn2. Notably, impaired regulation of the PFN1C71G skeletal muscle transcriptome exceeds that of the spinal cord and also improved by Atxn2 reduction in the CNS. Lastly, we find significant gene co-expression network homology between PFN1C71G mice and human ALS, with shared dysregulation of modules related to neuroinflammation and neuronal function and uncover novel hub genes that provide biological insight into ALS and potential drug targets that can be further investigated in this mouse model.
Published in
Viral-mediated knockdown of Atxn2 attenuates TDP-43 pathology and muscle dysfunction in the PFN1(C71G) ALS mouse model
Hawley ZCE, Li X, Bodnar D et al. · Acta neuropathologica communications 2025 · PMID 40413526 · doi:10.1186/s40478-025-02005-z
This dataset
Open GSE297399 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 GSE297399_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 PRJNA1263757 and SRA study SRP585902. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40413526) ↗
Study design
9 conditions, mostly with about 6 replicates each
FVB_WT_SC_Vehicle ×6 PFN1_C71G_SC_Vehicle ×6 PFN1_C71G_SC_amiR_ATXN2 ×6 PFN1_C71G_CTX_Vehicle ×6 PFN1_C71G_CTX_amiR_ATXN2 ×6 FVB_WT_SKM_Vehicle ×6 PFN1_C71G_SKM_amiR_ATXN2 ×6 FVB_WT_CTX_Vehicle ×5 +1 more

Supports a between-group comparison across 52 samples.

How we read this: 9 replicated groups read from 52 sample titles; they account for 52 of them. 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

+ 12 more — browse all 52 samples with per-sample file links →

Datasets on a similar topic

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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.