GEO series

Selective targeting of mutant huntingtin intron-1 improves rescue provided by antisense oligonucleotides in HTT.Q111/+ mice

GSE296071 Mus musculus (mouse) RNA-seq (gene expression) 30 samples Submitted 2025/06/30 Platform GPL13112

At a glance

RNA-seq (gene expression) · mouse · 30 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: 30 samples: 12 conditions, mostly in triplicateGroups 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)

Huntington’s disease (HD) arises from the toxic gain of function caused by a CAG expansion in the coding region of the HTT gene. HD is increasingly appreciated to emerge from multiple pathogenic processes, including somatic instability in mutant HTT’s (mHTT) CAG repeat tract, which leads to diverse deleterious consequences. These include the alternative processing of HTT pre-mRNA to generate the HTT1a transcript that encodes the very toxic, mHTT isoform referred to as HTT1a.

Read the full summary ↓

We set out to compare the efficacy and safety of allele-selective lowering of mHTT compared to non-allele-selective lowering using antisense oligonucleotides (ASOs) in heterozygous HttQ111 (Q111) mice. We developed a mutant specific ASO (MutASO) targeting Htt intron-1 that selectively reduced mutant full-length HTT, as well as HTT1a, in the brains of Q111 mice. Compared to the rescue provided by a pan-allele-targeting ASO (PanASO) that lowers wild-type HTT and full-length mHTT (sparing HTT1a), the MutASO essentially eliminated aggregate formation, and provided marked protection from transcriptional dysregulation in HD knock-in mice. Thus, by targeting the ASO to the region upstream of the cryptic polyadenylation sites required to generate the HTT1a transcript, our allele-selective MutASO potently reduced HTT1a protein levels. Here, our findings advocate that HTT1a may have a disproportionate impact on aggregate formation and transcriptional dysregulation and that lowering the levels of HTT1a should be included in the design of HTT-lowering based therapeutic strategies for HD.

This dataset

Open GSE296071 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 GSE296071_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 PRJNA1257448 and SRA study SRP582488. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

12 conditions, mostly in triplicate

M, WT, Saline, ×3 M, WT, Mut_ASO, ×3 M, Q111, Saline, ×3 M, Q111, Mut_ASO, ×3 M, Q111, Pan_ASO, ×3 M, WT, Pan_ASO, ×3 F, Q111, Saline, ×2 F, Q111, Pan_ASO, ×2 +4 more

Supports a between-group comparison across 30 samples.

How we read this: 12 replicated groups read from 30 sample titles; they account for 30 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

GSM8964609 M, WT, Saline, Rep 1 M, WT, Saline,
GSM8964610 M, WT, Mut_ASO, Rep 1 M, WT, Mut_ASO,
GSM8964611 M, Q111, Saline, Rep 1 M, Q111, Saline,
GSM8964612 M, Q111, Mut_ASO, Rep 1 M, Q111, Mut_ASO,
GSM8964613 F, Q111, Saline, Rep 4 F, Q111, Saline,
GSM8964614 F, Q111, Pan_ASO, Rep 4 F, Q111, Pan_ASO,
GSM8964615 F, WT, Mut_ASO, Rep 4 F, WT, Mut_ASO,
GSM8964616 M, Q111, Pan_ASO, Rep 1 M, Q111, Pan_ASO,
GSM8964617 M, Q111, Pan_ASO, Rep 2 M, Q111, Pan_ASO,
GSM8964618 M, Q111, Mut_ASO, Rep 2 M, Q111, Mut_ASO,
GSM8964619 M, Q111, Saline, Rep 2 M, Q111, Saline,
GSM8964620 M, Q111, Saline, Rep 3 M, Q111, Saline,
GSM8964621 M, Q111, Pan_ASO, Rep 3 M, Q111, Pan_ASO,
GSM8964622 M, Q111, Mut_ASO, Rep 3 M, Q111, Mut_ASO,
GSM8964623 M, WT, Saline, Rep 2 M, WT, Saline,
GSM8964624 M, WT, Saline, Rep 3 M, WT, Saline,
GSM8964625 M, WT, Pan_ASO, Rep 1 M, WT, Pan_ASO,
GSM8964626 M, WT, Pan_ASO, Rep 2 M, WT, Pan_ASO,
GSM8964627 M, WT, Mut_ASO, Rep 2 M, WT, Mut_ASO,
GSM8964628 M, WT, Mut_ASO, Rep 3 M, WT, Mut_ASO,
GSM8964629 M, WT, Pan_ASO, Rep 3 M, WT, Pan_ASO,
GSM8964630 F, WT, Mut_ASO, Rep 5 F, WT, Mut_ASO,
GSM8964631 F, WT, Saline, Rep 4 F, WT, Saline,
GSM8964632 F, WT, Saline, Rep 5 F, WT, Saline,
GSM8964633 F, WT, Pan_ASO, Rep 4 F, WT, Pan_ASO,
GSM8964634 F, WT, Pan_ASO, Rep 5 F, WT, Pan_ASO,
GSM8964635 F, Q111, Saline, Rep 5 F, Q111, Saline,
GSM8964636 F, Q111, Pan_ASO, Rep 5 F, Q111, Pan_ASO,
GSM8964637 F, Q111, Mut_ASO, Rep 4 F, Q111, Mut_ASO,
GSM8964638 F, Q111, Mut_ASO, Rep 5 F, Q111, Mut_ASO,

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