ArticlePLoS genetics2012
The App-Runx1 region is critical for birth defects and electrocardiographic dysfunctions observed in a Down syndrome mouse model.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- ADAM19: biological characteristics and implications in disease pathology and clinical applications.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Neuronal oscillations in cognition: Down syndrome as a model of mouse to human translation.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025Review
- 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
- SLC5A3 is important for cervical cancer cell growth.International journal of biological sciences · 2023Article
- Cell models for Down syndrome-Alzheimer's disease research.Neuronal signaling · 2022Review
- Cardiovascular physiology and pathophysiology in Down syndrome.Physiological research · 2022Article
- Circulating microRNA: Myocardium-derived prenatal biomarker of ventricular septal defects.Frontiers in genetics · 2022Article
- Comprehensive phenotypic analysis of the Dp1Tyb mouse strain reveals a broad range of Down syndrome-related phenotypes.Disease models & mechanisms · 2021Article
- Network analysis of Down syndrome and SARS-CoV-2 identifies risk and protective factors for COVID-19.Scientific reports · 2021Article
- Heart rate and blood pressure in male Ts65Dn mice: a model to investigate cardiovascular responses in Down syndrome.Physiological reports · 2019Article
- Rodent models in Down syndrome research: impact and future opportunities.Disease models & mechanisms · 2017Review
- Mouse-based genetic modeling and analysis of Down syndrome.British medical bulletin · 2016Review
- Aortic dilation, genetic testing, and associated diagnoses.Genetics in medicine : official journal of the American College of Medical Genetics · 2016Article
- Article
- Deletion of the App-Runx1 region in mice models human partial monosomy 21.Disease models & mechanisms · 2015Article
- Dosage of the Abcg1-U2af1 region modifies locomotor and cognitive deficits observed in the Tc1 mouse model of Down syndrome.PloS one · 2015Article
- Stem and progenitor cell dysfunction in human trisomies.EMBO reports · 2015Review
- Increased P-wave and QT dispersions necessitate long-term follow-up evaluation of Down syndrome patients with congenitally normal hearts.Pediatric cardiology · 2014Article
- Cognition and hippocampal plasticity in the mouse is altered by monosomy of a genomic region implicated in Down syndrome.Genetics · 2014Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Down syndrome (DS) leads to complex phenotypes and is the main genetic cause of birth defects and heart diseases. The Ts65Dn DS mouse model is trisomic for the distal part of mouse chromosome 16 and displays similar features with post-natal lethality and cardiovascular defects. In order to better understand these defects, we defined electrocardiogram (ECG) with a precordial set-up, and we found conduction defects and modifications in wave shape, amplitudes, and durations in Ts65Dn mice. By using a genetic approach consisting of crossing Ts65Dn mice with Ms5Yah mice monosomic for the App-Runx1 genetic interval, we showed that the Ts65Dn viability and ECG were improved by this reduction of gene copy number. Whole-genome expression studies confirmed gene dosage effect in Ts65Dn, Ms5Yah, and Ts65Dn/Ms5Yah hearts and showed an overall perturbation of pathways connected to post-natal lethality (Coq7, Dyrk1a, F5, Gabpa, Hmgn1, Pde10a, Morc3, Slc5a3, and Vwf) and heart function (Tfb1m, Adam19, Slc8a1/Ncx1, and Rcan1). In addition cardiac connexins (Cx40, Cx43) and sodium channel sub-units (Scn5a, Scn1b, Scn10a) were found down-regulated in Ts65Dn atria with additional down-regulation of Cx40 in Ts65Dn ventricles and were likely contributing to conduction defects. All these data pinpoint new cardiac phenotypes in the Ts65Dn, mimicking aspects of human DS features and pathways altered in the mouse model. In addition they highlight the role of the App-Runx1 interval, including Sod1 and Tiam1, in the induction of post-natal lethality and of the cardiac conduction defects in Ts65Dn. These results might lead to new therapeutic strategies to improve the care of DS people.
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