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A novel Adnp frameshift variant disrupts Wnt signaling leading to chromatocytoskeletal defects and autism-related behavior in mice

GSE319683 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 26 samples Submitted 2026/02/18 Platform GPL24247Platform GPL28457
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 26 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Mus musculus (mouse)
Samples
26 samples: 6 conditions, mostly with about 7 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
An Adnp frameshift variant disrupts Wnt signalling inducing chromatocytoskeletal defects and autism-related behaviour in male miceEBioMedicine · 2026
Summary (written by the submitters)
Background: Heterozygous de novo variants in the transcription factor Activity-Dependent Neuroprotective Protein (ADNP) cause a severe neurodevelopmental disorder, termed the Helsmoortel-Van der Aa syndrome (HVDAS), that is characterized by autism, intellectual delay, and malfunctions in several other organ systems. The ADNP gene is essential for embryonic development and interacts with components of several chromatin remodeling complexes, though the exact pathophysiological mechanisms remain hidden.
Read the full summary ↓
Methods: We used CRISPR/Cas9 genome editing to create a 14-base pair deletion in the murine Adnp gene to study the effects of the variant in a heterozygous disease-relevant mouse model. Results: Heterozygous mice carrying the c.2463_2476del (p.Leu822Hisfs*6) deletion are viable and fertile. Introduction of the 14-base pair deletion reduced cellular Adnp levels in the brain as well as its associations to chromatin, paralleled by a genome-wide increase in chromatin accessibility. Morphology analysis showed mild neuroanatomical changes in brain regions related to cognition, memory and learning, and motor skills. Behavioral testing in heterozygous Adnp mice confirmed cognitive defects in the Morris water maze test, increased anxiety in the elevated plus maze test, repetitive behavior after marble burying, and impaired social interactions. Transcriptome sequencing of the frontal cortex, an essential region involved in executive functions, cognition, and motor control, showed predominant downregulation of the Wnt signaling pathway. Cytoskeletal abnormalities were further coupled to synaptic plasticity deficits with dysregulated transcription factors implicated in lineage specification, as well as alterations in neuronal cell numbers. Adnp can also directly regulated mechanisms of synaptic plasticity by interacting with Camk2a and Dbn1. The frameshift variant interfered with these complexes and caused aberrant Camk2a phosphorylation at synapses. Mass spectrometry of the frontal cortex of heterozygous Adnp mice identified changes of multiple chromatin interacting proteins and cytoskeletal components, confirming chromatocytoskeletal dysregulations detected in the bulk transcriptome. Ultimately, Hi-C analysis detected fine-scale, locus-specific differences in 3D genome architecture in the heterozygous Adnp 14-base pair deletion mice, which are associated with transcriptional changes. Conclusions: We generated a disease-relevant heterozygous Adnp mouse model that parallels many of the molecular and behavioral aspects observed in Helsmoortel-Van der Aa patients. We demonstrate that Adnp has a primary nuclear role involving Wnt signaling coupled with cytoskeletal deficits. Our novel mouse model is thus a valuable model to study the human disorder and may be used for preclinical studies.
Published in
An Adnp frameshift variant disrupts Wnt signalling inducing chromatocytoskeletal defects and autism-related behaviour in male mice
D'Incal CP, Cappuyns E, Paldi F et al. · EBioMedicine 2026 · PMID 42208149 · doi:10.1016/j.ebiom.2026.106309
This dataset
Open GSE319683 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 GSE319683_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1424944 and SRA study SRP677726. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42208149) ↗
Study design
6 conditions, mostly with about 7 replicates each
Mouse, ANDP Mutant ×7 Mouse, ANDP Wild-Type ×7 Mouse, ADNP Mutant ×3 Mouse, ADNP Wild-Type ×3 ADNP Mutant Sample ×2 ADNP Wild-Type ×2 Mouse, ADNP PAT ×1 Mouse, Control ×1

Supports a case/control comparison: 12 samples read as cases, 13 as controls.

How we read this: 6 replicated groups read from 26 sample titles; they account for 24 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
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