The phenotypes of M21 are variable among individuals and depend on the specific deleted region of Hsa21. The remaining M21 cases are partial deletion or mosaics. Full M21 is rare and generally not compatible with life, with only a few cases reported in literature, and the oldest case survived for only a few days after birth. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist.ĭS and M21 are complex genetic conditions that arise from an altered dosage of genes on human chromosome 21 (Hsa21). This study been supported by French state funds through the “Agence Nationale de la Recherche” under the frame programme Investissements d’Avenir labelled ANR-10-IDEX-0002-02, ANR-10-LABX-0030-INRT, ANR-10-INBS-07 PHENOMIN. The laboratory of SEA was supported by grants from The Swiss National Science Foundation (144082), the EU AnEUploidy project (LSHG-CT-2006-037627), and the ERC (249968). This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedĭata Availability: Data from the expression study are under the GEO accession number (GSE58463).įunding: The project was supported by the French National Centre for Scientific Research (CNRS), the French National Institute of Health and Medical Research (INSERM), the University of Strasbourg and the “Centre Europeen de Recherche en Biomedecine”, the “Fondation Jerome Lejeune”, and the European commission (AnEUploidy project LSHG-CT-2006-037627 to YH, MD and SEA). Received: JAccepted: FebruPublished: March 24, 2015Ĭopyright: © 2015 Brault et al. Barsh, Stanford University School of Medicine, United States (2015) Opposite Phenotypes of Muscle Strength and Locomotor Function in Mouse Models of Partial Trisomy and Monosomy 21 for the Proximal Hspa13-App Region. Our results indicate that the copy number variation in the Hspa13-App region has a peripheral impact on locomotor activity by altering muscle function.Ĭitation: Brault V, Duchon A, Romestaing C, Sahun I, Pothion S, Karout M, et al. Thus, we demonstrated how the Hspa13-App interval controls metabolic and mitochondrial phenotypes in muscles certainly as a consequence of change in dose of Gabpa, Nrip1, and Atp5j. However, the reactive oxygen species (ROS) production from mitochondrial complex I decreased in Ms3Yah mice, while the membrane permeability of Ts3Yah mitochondria slightly increased. The shift in skeletal muscle metabolism correlates with a change in mitochondrial proliferation without an alteration in the respiratory function. These genes are downregulated in Ts3Yah mice and upregulated in Ms3Yah mice. The expression profiling of skeletal muscles revealed global changes in the regulation of genes implicated in energetic metabolism, mitochondrial activity, and biogenesis. Here we report that the trisomy and the monosomy of this region alter locomotion, muscle strength, mass, and energetic balance. To search for dosage-sensitive genes involved in DS and M21 phenotypes, we created two new mouse models: the Ts3Yah carrying a tandem duplication and the Ms3Yah carrying a deletion of the Hspa13-App interval syntenic with 21q11.2-q21.3. Both conditions lead to variable physiological abnormalities with constant intellectual disability, locomotor deficits, and altered muscle tone. In contrast to trisomy, the complete monosomy (M21) of Hsa21 is lethal, and only partial monosomy or mosaic monosomy of Hsa21 is seen. The trisomy of human chromosome 21 (Hsa21), which causes Down syndrome (DS), is the most common viable human aneuploidy.
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