Opposite phenotypes of muscle strength and locomotor function in mouse models of partial trisomy and monosomy 21 for the proximal Hspa13-App region

The trisomy of human chromosome 21 (Hsa21), which causes Down syndrome (DS), is the most common viable human aneuploidy. In contrast to trisomy, the complete monosomy (M21) of Hsa21 is lethal, and only partial monosomy or mosaic monosomy of Hsa21 is seen. Both conditions lead to variable physiological abnormalities with constant intellectual disability, locomotor deficits, and altered muscle tone. 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. Here we report that the trisomy and the monosomy of this region alter locomotion, muscle strength, mass, and energetic balance. The expression profiling of skeletal muscles revealed global changes in the regulation of genes implicated in energetic metabolism, mitochondrial activity, and biogenesis. These genes are downregulated in Ts3Yah mice and upregulated in Ms3Yah mice. The shift in skeletal muscle metabolism correlates with a change in mitochondrial proliferation without an alteration in the respiratory function. However, the reactive oxygen species (ROS) production from mitochondrial complex I decreased in Ms3Yah mice, while the membrane permeability of Ts3Yah mitochondria slightly increased. 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. Our results indicate that the copy number variation in the Hspa13-App region has a peripheral impact on locomotor activity by altering muscle function.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/nLSHG-CT-2006-037627 to YH, MD and SEA). 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 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

Polymer–Ceramic Nanohybrid Materials

This review is dedicated to nanohybrid materials consisting of a polymer-based matrix and a disperse nanoscaled ceramic phase. Different preparation techniques for the synthesis of polymer–ceramic nanohybrid materials will be presented, such as blending techniques, sol–gel processing, in-situ polymerization, and self-assembly methods. Selected structural and functional properties of polymer–ceramic nanohybrid materials will be highlighted and discussed within the context of their dependence on parameters such as the homogeneity of the dispersion of the ceramic throughout the polymer matrix, the particle size of the ceramic phase, and the polymer–ceramic interface. Moreover, some advanced applications of polymer–ceramic nanohybrid materials will be addressed and compared with their polymeric counterparts