ArticleMolecular metabolism2023
Dysregulated systemic metabolism in a Down syndrome mouse model.
Article in Molecular metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Gene dosage imbalance disrupts systemic metabolism in the Dp16 Down syndrome mouse model.eLife · 2026Article
- Endocrine and Digestive Disorders Arising in Childhood in Down Syndrome and Their Cross-Talk.Nutrients · 2026Review
- Promoting Research Excellence in Down Syndrome: Proceedings of the 5th International Conference of the Trisomy 21 Research Society.Neuromolecular medicine · 2026Article
- Genetic analysis of triplicated genes affecting sex-specific skeletal deficits in Down syndrome model mice.G3 (Bethesda, Md.) · 2026Article
- Genome-wide cell type-specific and sex-specific transcriptional dysregulation in the islet of Langerhans underlies islet dysfunction in Down syndrome-related diabetes.bioRxiv : the preprint server for biology · 2026Article
- Altered hepatic metabolism in Down syndrome.Cell reports · 2026Article
- Gene dosage imbalance disrupts systemic metabolism in the Dp16 Down syndrome mouse model.bioRxiv : the preprint server for biology · 2026Article
- Role of cystathionine-β-synthase and hydrogen sulfide in down syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
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- Carbonyl reductase 1: a novel regulator of blood pressure in Down syndrome.Bioscience reports · 2025Article
- A Pathway-Level Information ExtractoR (PLIER) framework to gain mechanistic insights into obesity in Down syndrome.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2025Article
- Assessing the Benefit of Dietary Choline Supplementation Throughout Adulthood in the Ts65Dn Mouse Model of Down Syndrome.Nutrients · 2024Article
- Body composition parameters and sarcopenia in adults with Down syndrome: a case-control study.Aging clinical and experimental research · 2024Article
- Senescent hearts from male Ts65Dn mice exhibit preserved function but altered size and nicotinamide adenine dinucleotide pathway signaling.American journal of physiology. Regulatory, integrative and comparative physiology · 2024Article
- Developmental deglutition and intrinsic tongue muscle maturation phenotypes in the Ts65Dn mouse model of Down syndrome.Frontiers in neurology · 2024Article
- Brain Mitochondrial Bioenergetics in Genetic Neurodevelopmental Disorders: Focus on Down, Rett and Fragile X Syndromes.International journal of molecular sciences · 2023Review
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- Hypermetabolism in mice carrying a near complete human chromosome 21.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveTrisomy 21 is one of the most complex genetic perturbations compatible with postnatal survival. Dosage imbalance arising from the triplication of genes on human chromosome 21 (Hsa21) affects multiple organ systems. Much of Down syndrome (DS) research, however, has focused on addressing how aneuploidy dysregulates CNS function leading to cognitive deficit. Although obesity, diabetes, and associated sequelae such as fatty liver and dyslipidemia are well documented in the DS population, only limited studies have been conducted to determine how gene dosage imbalance affects whole-body metabolism. Here, we conduct a comprehensive and systematic analysis of key metabolic parameters across different physiological states in the Ts65Dn trisomic mouse model of DS.
methodsTs65Dn mice and euploid littermates were subjected to comprehensive metabolic phenotyping under basal (chow-fed) state and the pathophysiological state of obesity induced by a high-fat diet (HFD). RNA sequencing of liver, skeletal muscle, and two major fat depots were conducted to determine the impact of aneuploidy on tissue transcriptome. Pathway enrichments, gene-centrality, and key driver estimates were performed to provide insights into tissue autonomous and non-autonomous mechanisms contributing to the dysregulation of systemic metabolism.
resultsUnder the basal state, chow-fed Ts65Dn mice of both sexes had elevated locomotor activity and energy expenditure, reduced fasting serum cholesterol levels, and mild glucose intolerance. Sexually dimorphic deterioration in metabolic homeostasis became apparent when mice were challenged with a high-fat diet. While obese Ts65Dn mice of both sexes exhibited dyslipidemia, male mice also showed impaired systemic insulin sensitivity, reduced mitochondrial activity, and elevated fibrotic and inflammatory gene signatures in the liver and adipose tissue. Systems-level analysis highlighted conserved pathways and potential endocrine drivers of adipose-liver crosstalk that contribute to dysregulated glucose and lipid metabolism.
conclusionsA combined alteration in the expression of trisomic and disomic genes in peripheral tissues contribute to metabolic dysregulations in Ts65Dn mice. These data lay the groundwork for understanding the impact of aneuploidy on in vivo metabolism.
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