Functional characterization of a low‐density lipoprotein receptor in the lepidopteran model, Bombyx mori

The growth and development of metabolous insects are mainly regulated by ecdysone and juvenile hormone. As a member of the low‐density lipoprotein receptor (LDLR) family, megalin (mgl) is involved in the lipoprotein transport of cholesterol which is an essential precursor for the synthesis of ecdysone. Despite extensive studies in mammals, the function of mgl is still largely unknown in insects. In this study, we characterize the function of mgl in the silkworm Bombyx mori, the model species of Lepidoptera. We find that mgl is broadly present in the genomes of lepidopteran species and evolved with divergence between lepidopterans and Drosophila. The expression pattern suggests a ubiquitous role of mgl in the growth and development in the silkworm. We further perform clustered regularly interspaced palindromic repeats (CRISPR) / CRISPR‐associated protein 9‐based mutagenesis of Bmmgl and find that both the development and the silk production of the silkworm are seriously affected by the disruption of Bmmgl. Our results not only explore the function of mgl in Lepidoptera but also add to our understanding of how cholesterol metabolism is involved in the development of insects. Mgl encodes a low‐density lipoprotein receptor in insects. By mutagenesis of Bmmgl in the silkworm (the dashed box), the development of silkworms has been greatly affected in various aspects. In comparison to wildtype silkworms (WT), the mutants (Δmgl) show the prolonged periods in each larval instar, the evident defects in pupation, and the significant decreases in silk production.