PXD066807

PXD066807 is an original dataset announced via ProteomeXchange.

Title	Hepatocyte-specific Cas9-mediated editing of G6pc and Slc37a4 elicits comparable biochemical and regulatory responses between glycogen storage disease (GSD) type Ia and Ib mice
Description	Glycogen storage disease type I (GSD I) is an autosomal recessive inborn error of carbohydrate metabolism. Patients with GSD type Ia and Ib exhibit overlapping and distinct symptoms and complications. Notably, GSD Ia patients show more severe hypertriglyceridemia and higher risk of hepatic tumors than GSD Ib patients. Given the liver's pivotal role in these processes, this study utilized hepatocyte-specific CRISPR/Cas9-mediated gene editing to explore the pathophysiological and biochemical differences between hepatic GSD Ia and Ib. Additionally, hepatic histology, transcriptomics, and proteomics analysis was performed. Compared to controls, GSD Ia and Ib mice showed hepatomegaly, fasting hypoglycemia, hyperlactatemia, and increased uric acid in plasma, which was more pronounced in GSD Ia than Ib. Both GSD I subtypes showed similar reductions in hepatic acetyl-CoA precursor pool enrichment and inceases in de novo biosynthesis of hepatic stearate and oleate. Interestingly, only GSD Ia mice showed significantly elevated plasma triglyceride, uric acid, and hepatic phosphate sugars. These metabolic changes were reflected at the level of transcriptomics and proteomics results. Moreover, altered mRNAs and protein levels related to nucleotide-binding oligomerization domain (NOD) signaling pathways, infection and inflammation, liver disease, and chemical carcinogenesis were more pronounced in GSD Ia mice. Overall, the metabolic disturbance was more severe in hepatocyte-specific GSD Ia than Ib mice, consistent with the clinical phenotype on patients. The metabolic disorders and specific metabolites, genes, and proteins identified in this study provided new insights into the potential therapeutic targets for GSD I patients, highlighting the need for subtype-specific treatment strategies.
HostingRepository	PRIDE
AnnounceDate	2026-07-02
AnnouncementXML	Submission_2026-07-02_13:58:39.389.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Justina Clarinda Wolters
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-31 07:46:23	ID requested
⏵ 1	2026-07-02 13:58:40	announced

Krishnamurthy KA, Xiao R, Rutten MGS, Bos T, Bleeker A, Zhang M, de Vries HI, Koster M, Huijkman N, Smit M, Kloosterhuis N, Boer T, Schomakers B, van Weeghel M, van de Sluis B, Wolters JC, Bakker BM, Oosterveer MH, Hepatocyte-specific Cas9-mediated editing of G6pc and Slc37a4 elicits comparable biochemical and regulatory responses between glycogen storage disease (GSD) type Ia and Ib mice. Mol Metab, 110():102393(2026) [pubmed]

10.1016/j.molmet.2026.102393;

submitter keyword: mouse, proteomics, liver, GSD I

Dr. JC Wolters
contact affiliation	Laboratory of Pediatrics, UMCG, The Netherlands
contact email	j.c.wolters@umcg.nl
lab head
Justina Clarinda Wolters
contact affiliation	UMCG
contact email	j.c.wolters@umcg.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066807
     1. Label: PRIDE project
     2. Name: Hepatocyte-specific Cas9-mediated editing of G6pc and Slc37a4 elicits comparable biochemical and regulatory responses between glycogen storage disease (GSD) type Ia and Ib mice