Mutation in the FUS nuclear localisation signal domain causes neurodevelopmental and systemic metabolic alterations.
Mutation in the FUS nuclear localisation signal domain causes neurodevelopmental and systemic metabolic alterations.
复制标题
DOI：
10.1242/dmm.050200
复制
发表时间：
2023-10-01
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
--
作者：
Variants in the ubiquitously expressed DNA/RNA-binding protein FUS cause aggressive juvenile forms of amyotrophic lateral sclerosis (ALS). Most FUS mutation studies have focused on motor neuron degeneration; little is known about wider systemic or developmental effects. We studied pleiotropic phenotypes in a physiological knock-in mouse model carrying the pathogenic FUSDelta14 mutation in homozygosity. RNA sequencing of multiple organs aimed to identify pathways altered by the mutant protein in the systemic transcriptome, including metabolic tissues, given the link between ALS-frontotemporal dementia and altered metabolism. Few genes were commonly altered across all tissues, and most genes and pathways affected were generally tissue specific. Phenotypic assessment of mice revealed systemic metabolic alterations related to the pathway changes identified. Magnetic resonance imaging brain scans and histological characterisation revealed that homozygous FUSDelta14 brains were smaller than heterozygous and wild-type brains and displayed significant morphological alterations, including a thinner cortex, reduced neuronal number and increased gliosis, which correlated with early cognitive impairment and fatal seizures. These findings show that the disease aetiology of FUS variants can include both neurodevelopmental and systemic alterations. Summary: This work reinforces the fundamental role of FUS in neurodevelopment and systemic metabolism and the notion that the FUS gene should be considered in clinical neurodevelopmental genetic testing.
登录
查看更多内容
组蛋白 H2A 核/细胞质运输对于抗病毒免疫反应的负调节以及 TBK1 和 IRF3 的溶酶体降解至关重要
影响因子：
7.3
作者：
Wu XM;Fang H;Zhang J;Bi YH;Chang MX
通讯作者：
Chang MX
DOI：
10.1212/nxg.0000000000200011
发表时间：
2022-10
期刊：
Neurology. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
56.9
作者：
Kwiatkowski, T. J., Jr.;Bosco, D. A.;Brown, R. H., Jr.
通讯作者：
Brown, R. H., Jr.
DOI：
10.1080/21678421.2020.1733021
发表时间：
2020-02-28
影响因子：
2.8
作者：
Flies, C. M.;Veldink, J. H.
通讯作者：
Veldink, J. H.
反义寡核苷酸沉默将FUS表达作为肌萎缩性侧索硬化症的治疗方法。
影响因子：
82.9
作者：
Korobeynikov VA;Lyashchenko AK;Blanco-Redondo B;Jafar-Nejad P;Shneider NA
通讯作者：
Shneider NA