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Opposite Phenotypes of Muscle Strength and Locomotor Function in Mouse Models of Partial Trisomy and Monosomy 21 for the Proximal Region


Down syndrome is the most common genetic cause of intellectual disabilities, and marked hypotonia is among the constant diagnostic traits. Here we observe the opposite changes in locomotion, muscle strength, and energetic balance in new mouse models of DS and M21 for the Hspa13-App proximal region of human chromosome 21. The differential expression analysis revealed downregulation of skeletal muscle genes controlling energetic metabolism, mitochondrial activity, and biogenesis in Ts3Yah, while upregulation of similar set of genes was found in Ms3Yah mice. This phenomenon correlates with the changes in mitochondrial proliferation with increased membrane permeability of Ts3Yah mitochondria and decreased mitochondrial ROS production in Ms3Yah mice. Our results demonstrate the opposite phenotypic effect of trisomy and monosomy of the Hspa13-App syntenic region of human chromosome 21, highlighting new physiological mechanisms for hypotonia in DS individuals.


Vyšlo v časopise: Opposite Phenotypes of Muscle Strength and Locomotor Function in Mouse Models of Partial Trisomy and Monosomy 21 for the Proximal Region. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005062
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005062

Souhrn

Down syndrome is the most common genetic cause of intellectual disabilities, and marked hypotonia is among the constant diagnostic traits. Here we observe the opposite changes in locomotion, muscle strength, and energetic balance in new mouse models of DS and M21 for the Hspa13-App proximal region of human chromosome 21. The differential expression analysis revealed downregulation of skeletal muscle genes controlling energetic metabolism, mitochondrial activity, and biogenesis in Ts3Yah, while upregulation of similar set of genes was found in Ms3Yah mice. This phenomenon correlates with the changes in mitochondrial proliferation with increased membrane permeability of Ts3Yah mitochondria and decreased mitochondrial ROS production in Ms3Yah mice. Our results demonstrate the opposite phenotypic effect of trisomy and monosomy of the Hspa13-App syntenic region of human chromosome 21, highlighting new physiological mechanisms for hypotonia in DS individuals.


Zdroje

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Genetika Reprodukčná medicína

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PLOS Genetics


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