C9ORF72 deficiency results in degeneration of the zebrafish retina in vivo
bioRxiv (Cold Spring Harbor Laboratory)(2023)
摘要
G4C2 Hexanucleotide repeat expansions within the gene C9ORF72 are the most common cause of the neurodegenerative diseases Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD). This disease-causing expansion leads to a reduction in C9ORF72 expression levels in patients, suggesting haploinsufficiency could contribute to disease. To further understand the consequences of C9ORF72 deficiency in vivo , we generated a c9orf72 mutant zebrafish line. Analysis of the spinal cord revealed no appreciable neurodegenerative pathology such as loss of motor neurons, or increased levels of neuroinflammation. However, detailed examination of c9orf72-/- retinas showed prominent neurodegenerative features, including a decrease in retinal thickness, gliosis, and an overall reduction in neurons of all subtypes. Structurally, analysis of rod and cone cells within the photoreceptor layer showed a disturbance in the outer cells of the retina and rhodopsin mis-localisation from rod outer segments to their cell bodies and synaptic endings. Thus, C9ORF72 may play a previously unappreciated role in retinal homeostasis and suggests C9ORF72 deficiency can induce tissue specific neuronal loss.
### Competing Interest Statement
The authors have declared no competing interest.
更多查看译文
关键词
zebrafish retina,c9orf72 deficiency results
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要