Muscular tone and dosage effect of chromosome 21
The expression of genes involved in energetic metabolism regulation in muscles is decreased (blue) in Ts3Yah mice (trisomy) and increased (red) in Ms3Yah mice (monosomy) compared to wt mice (disomy). This leads to a decrease in the number of oxidative fibers (colored fibers) and mitochondria (arrows) in the skeletal muscles of trisomic mice, and an increase of oxidative fibers and mitochondria in the skeletal muscles of monosomic mice.
April 21, 2015
The trisomy of human chromosome 21, or Down syndrome, is the most common intellectual disability and leads also to locomotor deficits and altered muscle tone.
To search for genes involved in trisomy 21, the team of Yann Hérault at the IGBMC selected a specific segment of the chromosome 21 (Hspa13-App, normally present in two copies) and created two new mouse models, one with three copies (trisomy), the other with a single copy (monosomy).
This study, published March 24 2015 in PLOS Genetics, reveals that trisomy and monosomy of this region alter the muscle tone in an opposite way and, in skeletal muscles, the regulation of genes involved in energetic metabolism and mitochondrial activity. Researchers demonstrated that the shift in muscle metabolism correlates with a change in mitochondrial proliferation (increased in monosomy, decreased in trisomy).
Thus, this study demonstrated that the studied region (Hspa13-App) intervenes in mitochondrial and metabolic control of skeletal muscles and certainly participates to the hypotonia which is observed in trisomy 21.