5′-Nucleotidase Plays a Key Role in Uric Acid Metabolism of <i>Bombyx mori</i>

• Published in: Cells
• Main Authors: Linmeng Tang, Dehong Yang, Yaohui Wang, Xu Yang, Kai Chen, Xingyu Luo, Jun Xu, Yujia Liu, Zheng Tang, Qianqian Zhang, Zhiwei Liu, Yongping Huang
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Subjects: uric acid metabolism; 5′-nucleotidase; ABCG transporter; disease model; <i>Bombyx mori</i>
• Online Access: https://www.mdpi.com/2073-4409/10/9/2243

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 <i>Bombyx mori</i> has a homolog of the human gene that encodes the 5′-nucleotidase (5′N) involved in purine metabolism. The <i>B. mori</i> gene, <i>Bm5′N</i>, is located upstream of other genes involved in UA metabolism in the silkworm. Disruption of <i>Bm5′N</i> via the CRISPR/Cas9 system resulted in decreased UA levels in the silkworm epidermis and caused a translucent skin phenotype. When <i>Bm5′N</i> 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 <i>Bm5′N</i> mutants indicated that loss of the <i>Bm5′N</i> 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 <i>Bm5′N</i> 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.