Key Laboratory of Insect Developmental and Evolutionary Biology, Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China.
CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing 100049, China.
Cells. 2021 Aug 30;10(9):2243. doi: 10.3390/cells10092243.
Uric acid (UA) is the end-product in the human purine metabolism pathway. The UA that accumulates in silkworm tissues is excreted as a nitrogen waste product. Here, we first validated that has a homolog of the human gene that encodes the 5'-nucleotidase (5'N) involved in purine metabolism. The gene, , is located upstream of other genes involved in UA metabolism in the silkworm. Disruption of via the CRISPR/Cas9 system resulted in decreased UA levels in the silkworm epidermis and caused a translucent skin phenotype. When mutant silkworms were fed with the uric acid precursor inosine, the UA levels in the epidermis increased significantly. Furthermore, the metabolomic and transcriptomic analyses of mutants indicated that loss of the affected purine metabolism and the ABC transport pathway. Taken together, these results suggest that the UA pathway is conserved between the silkworm and humans and that the gene plays a crucial role in the uric acid metabolism of the silkworm. Thus, the silkworm may be a suitable model for the study of UA metabolism pathways relevant to human disease.
尿酸（UA）是人类嘌呤代谢途径的终产物。在蚕组织中积累的 UA 作为氮废物排出体外。在这里，我们首先验证了 具有编码参与嘌呤代谢的 5'-核苷酸酶（5'N）的人类基因的同源物。 基因 ，位于蚕中 UA 代谢相关其他基因的上游。通过 CRISPR/Cas9 系统破坏 导致蚕表皮中 UA 水平降低，并导致皮肤半透明表型。当 突变体蚕喂食尿酸前体肌苷时，表皮中的 UA 水平显著增加。此外， 突变体的代谢组学和转录组学分析表明， 基因的缺失影响了嘌呤代谢和 ABC 转运途径。总之，这些结果表明 UA 途径在蚕和人类之间是保守的， 基因在蚕的尿酸代谢中起着关键作用。因此，家蚕可能是研究与人类疾病相关的 UA 代谢途径的合适模型。
