Evidence map›Paper›PMID 42270039›Full record

ArticleMolecular metabolism2026

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.

Kishore A Krishnamurthy, Ruiqi Xiao, Martijn G S Rutten, Trijnie Bos, Aycha Bleeker, Mingjia Zhang, Hilda I de Vries, Mirjam Koster, Nicolette Huijkman, Marieke Smit and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Kishore A KrishnamurthyLaboratory of Pediatrics, University of Groningen, University Medical Center Groningen, the Netherlands; School of Pure and Applied Sciences, RV University, Mysore Campus, 571302, India.
Ruiqi XiaoLaboratory of Pediatrics, University of Groningen, University Medical Center Groningen, the Netherlands.
Martijn G S RuttenLaboratory of Cellular Senescence and Age-related Pathologies, European Research Institute for the Biology of Ageing, University Medical Center Groningen, the Netherlands.
Trijnie BosDepartment of Laboratory Medicine, University of Groningen, University Medical Center Groningen, the Netherlands.
Aycha BleekerLaboratory of Pediatrics, University of Groningen, University Medical Center Groningen, the Netherlands.
Mingjia ZhangLaboratory of Pediatrics, University of Groningen, University Medical Center Groningen, the Netherlands.
Hilda I de VriesLaboratory of Pediatrics, University of Groningen, University Medical Center Groningen, the Netherlands.
Mirjam KosterLaboratory of Pediatrics, University of Groningen, University Medical Center Groningen, the Netherlands.
Nicolette HuijkmanLaboratory of Pediatrics, University of Groningen, University Medical Center Groningen, the Netherlands.
Marieke SmitLaboratory of Pediatrics, University of Groningen, University Medical Center Groningen, the Netherlands.
Niels KloosterhuisLaboratory of Pediatrics, University of Groningen, University Medical Center Groningen, the Netherlands.
Theo BoerDepartment of Laboratory Medicine, University of Groningen, University Medical Center Groningen, the Netherlands.
Bauke SchomakersLaboratory Genetic Metabolic Diseases, UMC Amsterdam, the Netherlands; Core Facility Metabolomics, UMC Amsterdam, the Netherlands.
Michel van WeeghelLaboratory Genetic Metabolic Diseases, UMC Amsterdam, the Netherlands; Core Facility Metabolomics, UMC Amsterdam, the Netherlands.
Bart van de SluisLaboratory of Pediatrics, University of Groningen, University Medical Center Groningen, the Netherlands.
Justina C WoltersLaboratory of Pediatrics, University of Groningen, University Medical Center Groningen, the Netherlands; United for Metabolic Diseases (UMD), the Netherlands.
Barbara M BakkerLaboratory of Pediatrics, University of Groningen, University Medical Center Groningen, the Netherlands; United for Metabolic Diseases (UMD), the Netherlands. Electronic address: b.m.bakker01@umcg.nl.
Maaike H OosterveerLaboratory of Pediatrics, University of Groningen, University Medical Center Groningen, the Netherlands; Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, the Netherlands; United for Metabolic Diseases (UMD), the Netherlands; Therapy Accelerator for Rare Diseases, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address: Maaike.Oosterveer@radboudumc.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND/

objectiveGlycogen 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.

methodsGiven the liver's pivotal role in these processes, this study utilized hepatocyte-specific CRISPR/Cas9-mediated somatic gene editing to explore the pathophysiological and biochemical adaptations in hepatic GSD Ia and Ib side-by-side. Additionally, hepatic histology, transcriptomics, and proteomics analysis was performed.

resultsCompared to controls, hepatic GSD Ia and Ib mice showed hepatomegaly, fasting hypoglycemia, hyperlactatemia, and increased uric acid in plasma, which was somewhat more pronounced in GSD Ia than Ib. Both GSD I subtypes showed similar reductions in hepatic acetyl-CoA precursor pool enrichment and increases in de novo biosynthesis of hepatic stearate and oleate. Interestingly, only GSD Ia mice showed mildly elevated plasma triglyceride and hepatic phosphate sugars. Metabolic changes were reflected at the transcriptomic and proteomic levels, with largely similar responses between GSD Ia and Ib livers. Moreover, altered mRNAs and protein levels related to nucleotide-binding oligomerization domain (NOD) signaling pathways, infection and inflammation, liver disease, and chemical carcinogenesis were somewhat more pronounced in hepatic GSD Ia than in GSD Ib mice.

conclusionsOverall, the metabolic disturbance was more severe in hepatocyte-specific GSD Ia than in GSD Ib mice, consistent with the clinical phenotype in patients. The metabolic disorders and specific metabolites, genes, and proteins identified in this study provided new insights into the pathophysiological and biochemical phenotypes of GSD I subtypes in the liver.

Indexed as

AntiportersGlucose-6-PhosphataseGlycogen Storage Disease Type IHepatocytesAnimalsCRISPR-Cas SystemsDisease Models, AnimalFemaleGene EditingHumansLiverMaleMiceProteomicsAntiportersGlucose-6-Phosphatasede novo fatty acid biosynthesisHepatic GSD Ia vs GSD IbInflammationLiver diseaseProteomicsSugar phosphatesTranscriptomics

Identifiers

PMID42270039
PMCPMC13316303

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.