GEO series

Transcriptomic analysis of miAtxn2 knockdown effects on lumbar spinal cord in the TAR4/4 sporadic ALS mouse model

GSE283631 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2025/05/15 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 16 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: 16 samples
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: AAV-based delivery of RNAi targeting ataxin-2 improves survival and pathology in TDP-43 miceNature communications · 2025

Summary (written by the submitters)

Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron death due to nuclear loss and cytoplasmic aggregation of the splice factor TDP-43. Pathologic TDP-43 associates with stress granules (SGs) and downregulating the SG-associated protein Ataxin-2 (Atxn2) using antisense oligonucleotides (ASOs) prolongs survival in the TAR4/4 sporadic ALS mouse model, a strategy that failed in clinical trials, likely due to inadequate target engagement.

Read the full summary ↓

Here, we used an AAV with potent motor neuron transduction to deliver optimized Atxn2-targeting miRNAs. Atxn2 knockdown was achieved throughout the central nervous system (CNS) at a dose 40x lower than used in other work. In TAR4/4 mice, miAtxn2 treatment increased mean (54%) and median (45%) survival and robustly improved strength-related measures. There was a corresponding reduction of lower motor neuron death as well as reduced inflammatory markers in both motor cortex and spinal cord, and phosphorylated TDP-43 was reduced to wildtype levels. Transcriptome-wide dysregulation in the TAR4/4 model recapitulated ALS-associated gene signatures that were rescued after Atxn2 reduction, identifying therapeutic mechanisms and potential biomarkers for translation. Additionally, in slow progressing hemizygous mice, treatment slowed disease progression and in ALS patient-derived lower motor neurons, our vector transduced >95% of cells at an MOI 4 logs lower than previously reported for AAV and reduced human ATXN2 in a dose-dependent manner. Cumulatively these data support the utility of AAV-mediated RNAi against Atxn2 as a robust and translatable treatment strategy for sporadic ALS.

Published in

AAV-based delivery of RNAi targeting ataxin-2 improves survival and pathology in TDP-43 mice

Amado DA, Robbins AB, Whiteman KR et al. · Nature communications 2025 · PMID 40562771 · doi:10.1038/s41467-025-60497-8

This dataset

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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 GSE283631_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 PRJNA1194654 and SRA study SRP549675. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40562771) ↗

Samples in this study

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+ 16 more — browse all 16 samples with per-sample file links →

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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.