Abstract
The silkworm, Bombyx mori L., is an important economic insect that has been domesticated for thousands of years to produce silk. It is our great interest to investigate the possibility of developing the B. mori as human disease model. We searched the orthologs of human disease associated genes in the B. mori by bi-directional best hits of BLAST and confirmed by searching the OrthoDB. In total, 5006 genes corresponding to 1612 kinds of human diseases had orthologs in the B. mori, among which, there are 25 genes associated with diabetes mellitus. Of these, we selected the insulin receptor gene of the B. mori (Bm-INSR) to study its expression in different tissues and at different developmental stages and tissues. Quantitative PCR showed that Bm-INSR was highly expressed in the Malpighian tubules but expressed at low levels in the testis. It was highly expressed in the 3rd and 4th instar larvae, and adult. We knocked down Bm-INSR expression using RNA interference. The abundance of Bm-INSR transcripts were dramatically reduced to ~4% of the control level at 6 days after dsRNA injection and the RNAi-treated B. mori individuals showed apparent growth inhibition and malformation such as abnormal body color in black, which is the typical symptom of diabetic patients. Our results demonstrate that B. mori has potential use as an animal model for diabetic mellitus research.
Highlights
Animal models are a helpful for studying molecular mechanisms of human disease as well as for drug testing
We obtained 69,040 protein sequences corresponding to 2629 kinds of human disorders from the database of Online Mendelian Inheritance in Man (OMIM) [37]
We found that 25 B. mori genes were orthologs of human genes associated with diabetes mellitus (Table 1)
Summary
Animal models are a helpful for studying molecular mechanisms of human disease as well as for drug testing. The silkworm has been widely used as the bioreactor to express human genes for producing drugs or vaccines [27,28,29] Because of these advantages, the B. mori has been successfully used to model human disorders such as Parkinson’s disease [30], and human sepiapterin reductase deficiency [31]. Glucose can stimulates the release of Bombyxin in B. mori [36] These studies suggest that it is possible to use the B. mori to model insulin-related human diseases such as diabetes.
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