PXD066252-1

PXD066252 is an original dataset announced via ProteomeXchange.

Title	Proteomics on am mouse model reveals phenotypic divergence from human disease
Description	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. 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.
HostingRepository	PRIDE
AnnounceDate	2025-10-20
AnnouncementXML	Submission_2025-10-20_03:57:19.646.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christine von Toerne
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-17 01:47:55	ID requested
⏵ 1	2025-10-20 03:57:20	announced

10.3389/FENDO.2025.1680893;

submitter keyword: LC-MS

Gerhard K. H. Przemeck
contact affiliation	Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health Neuherberg, Germany
contact email	gerhard.przemeck@helmholtz-munich.de
lab head
Christine von Toerne
contact affiliation	Helmholtz Zentrum München
contact email	vontoerne@helmholtz-muenchen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066252
     1. Label: PRIDE project
     2. Name: Proteomics on am mouse model reveals phenotypic divergence from human disease