Introduction: Down syndrome (DS) is caused by trisomy of human chromosome 21 (HSA21). Motor dysfunction due to hypotonia has limited labour productivity and have significant effects on socio-economic status in DS individuals. Ts1Cje, a mouse model of DS that exhibits muscle weakness was employed, to investigate the expression profile of selected trisomic and disomic genes involved in skeletal muscle structure and function. Methods: Quadriceps and triceps were harvested from the Ts1Cje (C57BL/6) postnatal day 60-70 mice and corresponding wild-type littermates. Total RNA extracted from these tissues was subjected for quantitative expression profiling of three trisomic genes (Itsn1, Synj1 and Rcan1) involved in neurotransmission and six disomic genes (Lamc1, Leprel1, Myl6b, Msn, Pgm5 and Tmod1) essential for maintenance of muscle structure and function. Real-time quantitative PCR method was used for the profiling. Results: Differential gene expression in DS is reflected by 1.5-fold or more increase in the level of expression as predicted by the gene dosage imbalance hypothesis. The analysis showed no significant changes in the expression level of trisomic genes (Itsn1, Synj1 and Rcan1). On contrary, disomic genes, Leprel1 and Pgm5, were upregulated for more than 1.5-fold in DS quadriceps whereas Lamc1, Myl6b and Pgm5 were upregulated for more than 1.5 fold in DS triceps as compared to the wild-type group. Conclusions: Our findings suggest that the dysregulation of Lamc1, Leprel1, Myl6b and Pgm5 genes is associated to muscle weakness seen in Ts1Cje and may play a role in molecular pathogenesis of muscle weakness in DS.
Ts1Cje is a mouse model of Down syndrome (DS) with partial triplication of chromosome 16, which encompasses a high number of human chromosome 21 (HSA21) orthologous genes. The mouse model exhibits muscle weakness resembling hypotonia in DS individuals. The effect of extra gene dosages on muscle weakness or hypotonia in Ts1Cje and DS individuals remains unknown. To identify molecular dysregulation of the skeletal muscle, we compared the transcriptomic signatures of soleus and extensor digitorum longus (EDL) muscles between the adult Ts1Cje and disomic littermates. A total of 166 and 262 differentially expressed protein-coding genes (DEGs) were identified in the soleus and EDL muscles, respectively. The partial trisomy of MMU16 in Ts1Cje mice has a greater effect on gene expression in EDL. Top-down clustering analysis of all DEGs for represented functional ontologies revealed 5 functional clusters in soleus associated with signal transduction, development of reproductive system, nucleic acid biosynthesis, protein modification and metabolism as well as regulation of gene expression. On the other hand, only 3 functional clusters were observed for EDL namely neuron and cell development, protein modification and metabolic processes as well as ion transport. A total of 11 selected DEGs were validated using qPCR (disomic DEGs: Mansc1; trisomic DEGs: Itsn1, Rcan1, Synj1, Donson, Dyrk1a, Ifnar1, Ifnar2, Runx1, Sod1 and Tmem50b). The validated DEGs were implicated in neuromuscular junction signalling (Itsn1, Syn1), oxidative stress (Sod1, Runx1) and chronic inflammation processes (Runx1, Rcan1, Ifnar1, Ifnar2). Other validated DEGs have not been well-documented as involved in the skeletal muscle development or function, thus serve as interesting novel candidates for future investigations. To our knowledge, the study was the first attempt to determine the transcriptomic profiles of both soleus and EDL muscles in Ts1Cje mice. It provides new insights on the possible disrupted molecular pathways associated with hypotonia in DS individuals.
Down syndrome (DS) is a genetic condition resulting from triplication of human chromosome (HSA)21. Besides intellectual disability, DS is frequently associated with hypotonia. Satellite cells are the resident cells that provides robust and remarkable regenerative capacity to the skeletal muscles, and its population size has been reported to be disease-associated. However, little is known about the population size of satellite cells in DS and the association of its intrinsic cellular functionality and hypotonia seen in DS. Here, we studied the Ts1Cje mouse, a DS murine model displays the muscle weakness characteristic. Satellite cell populations were immunostained with Pax7 and myonuclei numbers in the Ts1Cje extensor digitorum longus muscle were assessed. Their cellular function was further determined via in vitro assay in high-serum conditioned medium. Subsequently, the in vitro self-renewal, proliferative, and differentiation activities of these myogenic precursor cells were assessed after 24, 48, and 72h using Pax7, MyoD, and Ki67 immunomarkers. Our results showed that the population and functionality of Ts1Cje satellite cell did not differ significantly when compared to the wildtype cells isolated from disomic littermates. In conclusion, our findings indicated that intrinsic cellular functionality of the satellite cells, do not contribute to muscle weakness in Ts1Cje mouse.
Dye decolorization through biological treatment techniques has been gaining momentum as it is based on suspended and attached growth biomass in both batch and continuous modes. Hence, this review focused on the contribution of moving bed biofilm reactors (MBBR) in dye removal. MBBR have been demonstrated to be an excellent technology for pollution extraction, load shock resistance, and equipment size and energy consumption reduction. The review went further to highlight different biocarrier materials for biofilm development this review identified biochar as an innovative and environmentally friendly material produced through the application of different kinds of reusable or recyclable wastes and biowastes. Biochar as a carbonized waste biomass could be a better competitor and environmentally friendly substitute to activated carbon given its lower mass costs. Biochar can be easily produced particularly in rural locations where there is an abundance of biomass-based trash. Given that circular bioeconomy lowers dependency on natural resources by turning organic wastes into an array of useful products, biochar empowers the creation of competitive goods. Thus, biochar was identified as a novel, cost-effective, and long-term management strategy since it brings about several essential benefits, including food security, climate change mitigation, biodiversity preservation, and sustainability improvement. This review concludes that integrating two treatment methods could greatly lead to better color, organic matter, and nutrients removal than a single biological MBBR treatment process.