PubMed:19246455 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/19246455","sourcedb":"PubMed","sourceid":"19246455","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/19246455","text":"The silkworm mutant lemon (lemon lethal) is a potential insect model for human sepiapterin reductase deficiency.\nTetrahydrobiopterin (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.","tracks":[{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":528,"end":531},"obj":"gene:6697"},{"id":"T1","span":{"begin":606,"end":623},"obj":"disease:C0030567"},{"id":"T2","span":{"begin":560,"end":565},"obj":"gene:5072"},{"id":"T3","span":{"begin":606,"end":623},"obj":"disease:C0030567"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"}]},{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":112},"obj":"Sentence"},{"id":"T2","span":{"begin":113,"end":252},"obj":"Sentence"},{"id":"T3","span":{"begin":253,"end":327},"obj":"Sentence"},{"id":"T4","span":{"begin":328,"end":517},"obj":"Sentence"},{"id":"T5","span":{"begin":518,"end":624},"obj":"Sentence"},{"id":"T6","span":{"begin":625,"end":858},"obj":"Sentence"},{"id":"T7","span":{"begin":859,"end":983},"obj":"Sentence"},{"id":"T8","span":{"begin":984,"end":1202},"obj":"Sentence"},{"id":"T9","span":{"begin":1203,"end":1325},"obj":"Sentence"},{"id":"T10","span":{"begin":1326,"end":1578},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"},{"subj":"T8","pred":"source","obj":"sentences"},{"subj":"T9","pred":"source","obj":"sentences"},{"subj":"T10","pred":"source","obj":"sentences"}]},{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":4,"end":12},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":20,"end":25},"obj":"OrganismTaxon"},{"id":"T3","span":{"begin":27,"end":32},"obj":"OrganismTaxon"},{"id":"T4","span":{"begin":73,"end":78},"obj":"OrganismTaxon"},{"id":"T5","span":{"begin":522,"end":527},"obj":"OrganismTaxon"},{"id":"T6","span":{"begin":671,"end":676},"obj":"OrganismTaxon"},{"id":"T7","span":{"begin":678,"end":681},"obj":"OrganismTaxon"},{"id":"T8","span":{"begin":705,"end":710},"obj":"OrganismTaxon"},{"id":"T9","span":{"begin":719,"end":722},"obj":"OrganismTaxon"},{"id":"T10","span":{"begin":763,"end":771},"obj":"OrganismTaxon"},{"id":"T11","span":{"begin":772,"end":783},"obj":"OrganismTaxon"},{"id":"T12","span":{"begin":828,"end":833},"obj":"OrganismTaxon"},{"id":"T13","span":{"begin":968,"end":971},"obj":"OrganismTaxon"},{"id":"T14","span":{"begin":976,"end":979},"obj":"OrganismTaxon"},{"id":"T15","span":{"begin":1045,"end":1048},"obj":"OrganismTaxon"},{"id":"T16","span":{"begin":1246,"end":1249},"obj":"OrganismTaxon"},{"id":"T17","span":{"begin":1440,"end":1449},"obj":"OrganismTaxon"},{"id":"T18","span":{"begin":1458,"end":1461},"obj":"OrganismTaxon"},{"id":"T19","span":{"begin":1463,"end":1466},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"7091"},{"id":"A2","pred":"db_id","subj":"T2","obj":"2708"},{"id":"A3","pred":"db_id","subj":"T3","obj":"2708"},{"id":"A4","pred":"db_id","subj":"T4","obj":"9606"},{"id":"A5","pred":"db_id","subj":"T5","obj":"9606"},{"id":"A6","pred":"db_id","subj":"T6","obj":"2708"},{"id":"A7","pred":"db_id","subj":"T7","obj":"2708"},{"id":"A8","pred":"db_id","subj":"T8","obj":"2708"},{"id":"A9","pred":"db_id","subj":"T9","obj":"2708"},{"id":"A10","pred":"db_id","subj":"T10","obj":"7091"},{"id":"A11","pred":"db_id","subj":"T11","obj":"7091"},{"id":"A12","pred":"db_id","subj":"T12","obj":"9606"},{"id":"A13","pred":"db_id","subj":"T13","obj":"2708"},{"id":"A14","pred":"db_id","subj":"T14","obj":"2708"},{"id":"A15","pred":"db_id","subj":"T15","obj":"2708"},{"id":"A16","pred":"db_id","subj":"T16","obj":"2708"},{"id":"A17","pred":"db_id","subj":"T17","obj":"7091"},{"id":"A18","pred":"db_id","subj":"T18","obj":"2708"},{"id":"A19","pred":"db_id","subj":"T19","obj":"2708"},{"subj":"T1","pred":"source","obj":"NCBITAXON"},{"subj":"T2","pred":"source","obj":"NCBITAXON"},{"subj":"T3","pred":"source","obj":"NCBITAXON"},{"subj":"T4","pred":"source","obj":"NCBITAXON"},{"subj":"T5","pred":"source","obj":"NCBITAXON"},{"subj":"T6","pred":"source","obj":"NCBITAXON"},{"subj":"T7","pred":"source","obj":"NCBITAXON"},{"subj":"T8","pred":"source","obj":"NCBITAXON"},{"subj":"T9","pred":"source","obj":"NCBITAXON"},{"subj":"T10","pred":"source","obj":"NCBITAXON"},{"subj":"T11","pred":"source","obj":"NCBITAXON"},{"subj":"T12","pred":"source","obj":"NCBITAXON"},{"subj":"T13","pred":"source","obj":"NCBITAXON"},{"subj":"T14","pred":"source","obj":"NCBITAXON"},{"subj":"T15","pred":"source","obj":"NCBITAXON"},{"subj":"T16","pred":"source","obj":"NCBITAXON"},{"subj":"T17","pred":"source","obj":"NCBITAXON"},{"subj":"T18","pred":"source","obj":"NCBITAXON"},{"subj":"T19","pred":"source","obj":"NCBITAXON"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"19246455-4#10#13#gene6697","span":{"begin":528,"end":531},"obj":"gene6697"},{"id":"19246455-4#42#47#gene5072","span":{"begin":560,"end":565},"obj":"gene5072"},{"id":"19246455-4#88#105#diseaseC0030567","span":{"begin":606,"end":623},"obj":"diseaseC0030567"}],"relations":[{"id":"10#13#gene669788#105#diseaseC0030567","pred":"associated_with","subj":"19246455-4#10#13#gene6697","obj":"19246455-4#88#105#diseaseC0030567"},{"id":"42#47#gene507288#105#diseaseC0030567","pred":"associated_with","subj":"19246455-4#42#47#gene5072","obj":"19246455-4#88#105#diseaseC0030567"}],"attributes":[{"subj":"19246455-4#10#13#gene6697","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"19246455-4#42#47#gene5072","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"19246455-4#88#105#diseaseC0030567","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":79,"end":111},"obj":"Disease"},{"id":"T2","span":{"begin":560,"end":565},"obj":"Disease"},{"id":"T3","span":{"begin":606,"end":623},"obj":"Disease"},{"id":"T4","span":{"begin":834,"end":848},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0012994"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0011220"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0005180"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0012994"},{"subj":"T1","pred":"source","obj":"mondo_disease"},{"subj":"T2","pred":"source","obj":"mondo_disease"},{"subj":"T3","pred":"source","obj":"mondo_disease"},{"subj":"T4","pred":"source","obj":"mondo_disease"}]},{"project":"silkworm","denotations":[{"id":"T1","span":{"begin":4,"end":12},"obj":"Species:7091"},{"id":"T2","span":{"begin":20,"end":25},"obj":"Species:2708"},{"id":"T3","span":{"begin":27,"end":32},"obj":"Species:2708"},{"id":"T4","span":{"begin":73,"end":78},"obj":"Species:9606"},{"id":"T5","span":{"begin":91,"end":111},"obj":"Disease:MESH:C536415"},{"id":"T6","span":{"begin":113,"end":132},"obj":"Chemical:MESH:C003402"},{"id":"T7","span":{"begin":134,"end":137},"obj":"Chemical:MESH:C003402"},{"id":"T8","span":{"begin":224,"end":233},"obj":"Chemical:-"},{"id":"T9","span":{"begin":253,"end":256},"obj":"Chemical:MESH:C003402"},{"id":"T10","span":{"begin":331,"end":347},"obj":"Disease:MESH:D030342"},{"id":"T11","span":{"begin":351,"end":354},"obj":"Chemical:MESH:C003402"},{"id":"T12","span":{"begin":385,"end":420},"obj":"Disease:MESH:C562657"},{"id":"T13","span":{"begin":422,"end":425},"obj":"Gene:6697"},{"id":"T14","span":{"begin":464,"end":467},"obj":"Chemical:MESH:C003402"},{"id":"T15","span":{"begin":473,"end":495},"obj":"Chemical:MESH:D006160"},{"id":"T16","span":{"begin":522,"end":527},"obj":"Species:9606"},{"id":"T17","span":{"begin":528,"end":531},"obj":"Gene:6697"},{"id":"T18","span":{"begin":560,"end":565},"obj":"Gene:5072"},{"id":"T19","span":{"begin":606,"end":623},"obj":"Disease:MESH:D010300"},{"id":"T20","span":{"begin":671,"end":676},"obj":"Species:2708"},{"id":"T21","span":{"begin":678,"end":681},"obj":"Species:2708"},{"id":"T22","span":{"begin":705,"end":710},"obj":"Species:2708"},{"id":"T23","span":{"begin":719,"end":722},"obj":"Species:2708"},{"id":"T24","span":{"begin":763,"end":771},"obj":"Species:7091"},{"id":"T25","span":{"begin":772,"end":783},"obj":"Species:7091"},{"id":"T26","span":{"begin":828,"end":833},"obj":"Species:9606"},{"id":"T27","span":{"begin":834,"end":837},"obj":"Gene:6697"},{"id":"T28","span":{"begin":838,"end":857},"obj":"Disease:MESH:D030342"},{"id":"T29","span":{"begin":897,"end":900},"obj":"Gene:6697"},{"id":"T30","span":{"begin":907,"end":912},"obj":"Gene:100379197"},{"id":"T31","span":{"begin":968,"end":971},"obj":"Species:2708"},{"id":"T32","span":{"begin":976,"end":979},"obj":"Species:2708"},{"id":"T33","span":{"begin":1029,"end":1032},"obj":"Gene:6697"},{"id":"T34","span":{"begin":1045,"end":1048},"obj":"Species:2708"},{"id":"T35","span":{"begin":1226,"end":1229},"obj":"Chemical:MESH:C003402"},{"id":"T36","span":{"begin":1234,"end":1242},"obj":"Chemical:MESH:D004298"},{"id":"T37","span":{"begin":1246,"end":1249},"obj":"Species:2708"},{"id":"T38","span":{"begin":1352,"end":1357},"obj":"Gene:100379197"},{"id":"T39","span":{"begin":1400,"end":1403},"obj":"Chemical:MESH:C003402"},{"id":"T40","span":{"begin":1409,"end":1418},"obj":"Chemical:-"},{"id":"T41","span":{"begin":1440,"end":1449},"obj":"Species:7091"},{"id":"T42","span":{"begin":1458,"end":1461},"obj":"Species:2708"},{"id":"T43","span":{"begin":1463,"end":1466},"obj":"Species:2708"},{"id":"T44","span":{"begin":1553,"end":1556},"obj":"Gene:6697"},{"id":"T45","span":{"begin":1561,"end":1577},"obj":"Disease:MESH:D010661"}],"attributes":[{"subj":"T1","pred":"source","obj":"silkworm"},{"subj":"T2","pred":"source","obj":"silkworm"},{"subj":"T3","pred":"source","obj":"silkworm"},{"subj":"T4","pred":"source","obj":"silkworm"},{"subj":"T5","pred":"source","obj":"silkworm"},{"subj":"T6","pred":"source","obj":"silkworm"},{"subj":"T7","pred":"source","obj":"silkworm"},{"subj":"T8","pred":"source","obj":"silkworm"},{"subj":"T9","pred":"source","obj":"silkworm"},{"subj":"T10","pred":"source","obj":"silkworm"},{"subj":"T11","pred":"source","obj":"silkworm"},{"subj":"T12","pred":"source","obj":"silkworm"},{"subj":"T13","pred":"source","obj":"silkworm"},{"subj":"T14","pred":"source","obj":"silkworm"},{"subj":"T15","pred":"source","obj":"silkworm"},{"subj":"T16","pred":"source","obj":"silkworm"},{"subj":"T17","pred":"source","obj":"silkworm"},{"subj":"T18","pred":"source","obj":"silkworm"},{"subj":"T19","pred":"source","obj":"silkworm"},{"subj":"T20","pred":"source","obj":"silkworm"},{"subj":"T21","pred":"source","obj":"silkworm"},{"subj":"T22","pred":"source","obj":"silkworm"},{"subj":"T23","pred":"source","obj":"silkworm"},{"subj":"T24","pred":"source","obj":"silkworm"},{"subj":"T25","pred":"source","obj":"silkworm"},{"subj":"T26","pred":"source","obj":"silkworm"},{"subj":"T27","pred":"source","obj":"silkworm"},{"subj":"T28","pred":"source","obj":"silkworm"},{"subj":"T29","pred":"source","obj":"silkworm"},{"subj":"T30","pred":"source","obj":"silkworm"},{"subj":"T31","pred":"source","obj":"silkworm"},{"subj":"T32","pred":"source","obj":"silkworm"},{"subj":"T33","pred":"source","obj":"silkworm"},{"subj":"T34","pred":"source","obj":"silkworm"},{"subj":"T35","pred":"source","obj":"silkworm"},{"subj":"T36","pred":"source","obj":"silkworm"},{"subj":"T37","pred":"source","obj":"silkworm"},{"subj":"T38","pred":"source","obj":"silkworm"},{"subj":"T39","pred":"source","obj":"silkworm"},{"subj":"T40","pred":"source","obj":"silkworm"},{"subj":"T41","pred":"source","obj":"silkworm"},{"subj":"T42","pred":"source","obj":"silkworm"},{"subj":"T43","pred":"source","obj":"silkworm"},{"subj":"T44","pred":"source","obj":"silkworm"},{"subj":"T45","pred":"source","obj":"silkworm"}]},{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":79,"end":111},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":341,"end":347},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":560,"end":565},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":606,"end":623},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":834,"end":848},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0012994"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0008568"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0011220"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"0005180"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"0012994"},{"subj":"T1","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T2","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T3","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T4","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T5","pred":"source","obj":"PMID_GLOBAL"}]},{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":606,"end":615},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0001300"},{"subj":"T1","pred":"source","obj":"HP-phenotype"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"DisGeNET","color":"#ec93c6","default":true},{"id":"sentences","color":"#93e0ec"},{"id":"NCBITAXON","color":"#ecde93"},{"id":"DisGeNET5_gene_disease","color":"#c393ec"},{"id":"mondo_disease","color":"#93eca9"},{"id":"silkworm","color":"#ec9396"},{"id":"PMID_GLOBAL","color":"#93b0ec"},{"id":"HP-phenotype","color":"#caec93"}]}]}}