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• W4380576777 abstract "To explore the molecular pathological mechanism of liver metabolic disorder in severe spinal muscular atrophy (SMA).The transgenic mice with type Ⅰ SMA (Smn-/-SMN20tg/2tg) and littermate control mice (Smn+/-SMN20tg/2tg) were observed for milk suckling behavior and body weight changes after birth. The mice with type Ⅰ SMA mice were given an intraperitoneal injection of 20% glucose solution or saline (15 μL/12 h), and their survival time was recorded. GO enrichment analysis was performed using the RNA-Seq data of the liver of type Ⅰ SMA and littermate control mice, and the results were verified using quantitative real-time PCR. Bisulfite sequencing was performed to examine CpG island methylation level in Fasn gene promoter region in the liver of the neonatal mice.The neonatal mice with type Ⅰ SMA showed normal milk suckling behavior but had lower body weight than the littermate control mice on the second day after birth. Intraperitoneal injection of glucose solution every 12 h significantly improved the median survival time of type Ⅰ SMA mice from 9±1.3 to 11± 1.5 days (P < 0.05). Analysis of the RNA-Seq data of the liver showed that the expression of the target genes of PPARα related to lipid metabolism and mitochondrial β oxidation were down-regulated in the liver of type Ⅰ SMA mice. Type Ⅰ SMA mice had higher methylation level of the Fasn promoter region in the liver than the littermate control mice (76.44% vs 58.67%). In primary cultures of hepatocytes from type Ⅰ SMA mice, treatment with 5-AzaC significantly up-regulated the expressions of the genes related to lipid metabolism by over 1 fold (P < 0.01).Type Ⅰ SMA mice have liver metabolic disorder, and the down-regulation of the target genes of PPARα related to lipid and glucose metabolism due to persistent DNA methylation contributes to the progression of SMA." @default.
• W4380576777 created "2023-06-15" @default.
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• W4380576777 date "2023-05-20" @default.
• W4380576777 modified "2023-10-18" @default.
• W4380576777 title "[Molecular pathological mechanism of liver metabolic disorder in mice with severe spinal muscular atrophy]." @default.
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• W4380576777 doi "https://doi.org/10.12122/j.issn.1673-4254.2023.05.22" @default.
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