The silkworm mutant lemon (lemon lethal) is a potential insect model for human sepiapterin reductase deficiency

Yan Meng, Susumu Katsuma, Takaaki Daimon, Yutaka Banno, Keiro Uchino, Hideki Sezutsu, Toshiki Tamura, Kazuei Mita, Toru Shimada

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35 Citations (Scopus)

Abstract

Tetrahydrobiopterin (BH4) is an essential cofactor for aromatic acid hydroxylases, which control the levels of monoamine neurotransmitters. BH4 deficiency has been associated with many neuropsychological disorders. An inherited defect in BH4 biosynthesis is caused by the deficiency of sepiapterin reductase (SPR), which catalyzes the biosynthesis of BH4 from guanosine triphosphate at the terminal step. The human SPR gene has been mapped at the PARK3 locus, which is related to the onset of Parkinson disease. In this study, we report that mutant strains, lemon (lem) and its lethal allele lemon lethal (leml) with yellow body coloration, of the silkworm Bombyx mori could be used as the first insect model for human SPR deficiency diseases. We demonstrated that mutations in the SPR gene (BmSpr) were responsible for the irregular body coloration of lem and leml. Moreover, biochemical analysis revealed that SPR activity in leml larvae was almost completely diminished, resulting in a lethal phenotype that the larvae cannot feed and that die immediately after the first ecdysis. Oral administration of BH4 and dopamine to leml larvae effectively increased their survival rates and feeding abilities. Our data demonstrate that BmSPR plays a crucial role in the generation of BH4, and monoamine neurotransmitters in silkworms and the lem (lem1) mutant strains will be an invaluable resource to address many questions regarding SPR and BH4 deficiencies.

Original languageEnglish
Pages (from-to)11698-11705
Number of pages8
JournalJournal of Biological Chemistry
Volume284
Issue number17
DOIs
Publication statusPublished - Apr 24 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Meng, Y., Katsuma, S., Daimon, T., Banno, Y., Uchino, K., Sezutsu, H., Tamura, T., Mita, K., & Shimada, T. (2009). The silkworm mutant lemon (lemon lethal) is a potential insect model for human sepiapterin reductase deficiency. Journal of Biological Chemistry, 284(17), 11698-11705. https://doi.org/10.1074/jbc.M900485200