上海海洋大学学报2024，Vol.33Issue(2)：317-326,10.DOI:10.12024/jsou.20231204372
aldh3a2a敲除对斑马鱼体色的影响
Role of aldh3a2a on the body color formation in zebrafish
摘要
Abstract
This study investigated the significance of aldh3a2a in zebrafish pigment cell development and its impact on aldehyde metabolism and liver health.Using CRISPR/Cas9 technology,we successfully generated aldh3a2a knockout homozygous mutant lineages,resulting in reduced numbers of melanocytes,xanthophores and iridophores,csf1ra,pnp4a and itk were downregulated,and key genes in the melanin synthesis pathway,including mitfa,tyrp1b and kita,were also downregulated.Transcriptome analysis revealed changes in gene expression profiles,with downregulation of differential genes scd,lpla and aox5 in the steroid biosynthesis pathway,indicating the critical role of aldh3a2a in steroid biosynthesis.Transcriptomic analysis and qPCR combined study on the retinol metabolism pathway revealed that aldh3a2a can regulate raldh2,rxrab and aox5,indicating its certain influence on the signaling transduction of retinoic acid receptors.Additionally,aldh3a2a can regulate potassium channel protein kcns3b,suggesting its association with melanocyte function and potassium ion signaling.GO and KEGG enrichment analysis found widespread effects on pathways such as the cell cycle,homologous recombination,RNA degradation,RNA transport,p53 signaling pathway,eukaryotic ribosome biogenesis,DNA replication,base excision repair,aminoacyl-tRNA biosynthesis,cytoplasmic DNA sensing pathway,steroid biosynthesis,mismatch repair,steroid hormone biosynthesis,and aldarate metabolism in the mutant.Moreover,knockout of the aldh3a2a gene leads to significant accumulation of aldehydes in the body,causing cytotoxicity and resulting in abnormal enlargement of the liver,appearance of vacuoles within the liver,and characteristic weight gain,resembling symptoms of Sjögren-Larsson syndrome.This reveals the role of aldh3a2a in zebrafish and its relevance to human genetic diseases,which will contribute to a deeper understanding of its function and potential therapeutic targets in both zebrafish and humans.关键词
aldh3a2a基因敲除/色素细胞/视黄醇代谢通路/视黄酸代谢Key words
aldh3a2a gene knockout/pigment cell/retinol metabolic pathway/retinoic acid metabolism分类
农业科技引用本文复制引用
卢培钰,冯毅栋,鲍宝龙..aldh3a2a敲除对斑马鱼体色的影响[J].上海海洋大学学报,2024,33(2):317-326,10.基金项目
国家自然科学基金(31872546) （31872546）
