RRC ID 28697
Author Meng Y, Katsuma S, Daimon T, Banno Y, Uchino K, Sezutsu H, Tamura T, Mita K, Shimada T.
Title The silkworm mutant lemon (lemon lethal) is a potential insect model for human sepiapterin reductase deficiency.
Journal J Biol Chem
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 (lem(1)) 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 lem(l). Moreover, biochemical analysis revealed that SPR activity in lem(l) 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 lem(l) 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 (lem(l)) mutant strains will be an invaluable resource to address many questions regarding SPR and BH4 deficiencies.
Volume 284(17)
Pages 11698-705
Published 2009-4-24
DOI 10.1074/jbc.M900485200
PII M900485200
Description lem(黄体色)の原因遺伝子はBmSprである。BmSprはセピアプテリン還元酵素をコードする。l70、e36、r04、b602、およびf40および系統のlem個体のBmSprでは、エクソン3の内部に中途終始コドンを生じさせる同一の点変異が存在する。a65系統(leml/leml)では、BmSprのエクソン3の内部に27bpの挿入配列が存在する。
PMID 19246455
PMC PMC2670173
MeSH Alcohol Oxidoreductases / deficiency* Amino Acid Sequence Animals Bombyx / genetics* Bombyx / metabolism Cloning, Molecular DNA Primers / chemistry Disease Models, Animal Gene Expression Regulation, Developmental* Humans Insecta Models, Biological Models, Genetic Molecular Sequence Data Mutation* Sequence Homology, Amino Acid
IF 4.238
Times Cited 34
Silkworms l70 e36 r04 b602 f40 a65