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MODY PDX1P33T: A Mouse Model Reveals Phenotypic Divergence from Human Disease

GSE303047 Mus musculus (mouse) RNA-seq (gene expression) 11 samples Submitted 2025/10/13 Platform GPL34290
At a glance

RNA-seq (gene expression) · mouse · 11 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
11 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
MODY PDX1(P33T): a mouse model reveals phenotypic divergence from human diseaseFrontiers in endocrinology · 2025
Summary (written by the submitters)
Introduction: Maturity-onset Diabetes of the Young (MODY) is a rare form of diabetes and arises from mutations in key regulatory genes of the pancreatic beta-cell, leading to their functional impairment and early-onset diabetes. Research into PDX1-MODY, a form of MODY caused by mutations in the PDX1 gene, enhances understanding of gene-specific mechanisms underlying glucose dysregulation and provides insights into possible approaches to restore normal metabolic function.
Read the full summary ↓
However, no currently published mouse model accurately depicts the genetic cause of PDX1-MODY in human patients. Methods: Using CRISPR-Cas9 technology, we generated the first mouse model carrying one of the most prevalent pathological PDX1 point mutation found in human patients, P33T, and conducted an 18-week in vivo phenotyping experiment assessing homozygous PDX1P33T and wild-type littermates on both chow and high fat diet (HFD). Additionally, transcriptomic and proteomic analyses were performed on isolated pancreatic islets. Islet architecture was investigated via fluorescent microscopy. Result: Contrary to expectations, our comprehensive phenotypic analysis of the mouse model carrying the homozygous PDX1P33T point mutation revealed no significant differences in metabolic parameters compared to wild-type controls, and no pathological outcomes were observed as seen in human patients. Notably, male PDX1P33T mice exhibited an increase in islet size and number on chow diet but failed to adapt respectively on HFD. Discussion: Our work indicates substantial differences between mouse and human PDX1 function in the pancreas. Further refinement of animal models is necessary to better elucidate the pathophysiology of PDX1-MODY. Ultimately, this study emphasizes the complexities involved in translating human pathologies to animal models, serving as a reminder that findings generated in mice may not always be easily translated to humans.
Published in
MODY PDX1(P33T): a mouse model reveals phenotypic divergence from human disease
Harten A, Schmidtke MR, Giesert F et al. · Frontiers in endocrinology 2025 · PMID 41199860 · doi:10.3389/fendo.2025.1680893
This dataset
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.

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 GSE303047_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1293404 and SRA study SRP601829. Searching any of these in the dataset finder brings you back here.

Samples in this study

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+ 11 more — browse all 11 samples with per-sample file links →

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