Allele Dmel\Met²⁷

General Information
Symbol	Dmel\Met²⁷	Species	D. melanogaster
Name		FlyBase ID	FBal0089546
Feature type	allele	Associated gene	Dmel\Met

Allele class	loss of function allele
Mutagen	X ray, 60Co gamma ray, gamma ray
Recent Updates
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FB2013_03
FB2013_02
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Nature of the Allele
Allele class	loss of function allele (Wilson et al., 1998, Wilson and Ashok, 1998, Wilson et al., 2006)
Mutagen	60Co gamma ray (Wilson and Ashok, 1998) gamma ray (Wilson et al., 2006) X ray (Ashok et al., 1998)
Mutations Mapped to the Genome

Type Location Additional Notes References
Associated Sequence Data
DDBJ / EMBL / GenBank	DNA sequence Protein sequence Name

UniProtKB/Swiss-Prot
UniProtKB/TrEMBL

Progenitor genotype
Nature of the lesion	Statement Reference Probably a chromosomal break in the transcriptional regulatory region. (Wilson and Ashok, 1998)
Cytology
Phenotypic Data
Phenotypic Class
	chemical resistant (Wilson and Ashok, 1998, Wilson et al., 1998, Ashok et al., 1998, Wilson et al., 2006) chemical resistant \| larval stage (Abdou et al., 2011) female fertile \| reduced (Gruntenko et al., 2000) female semi-sterile (Abdou et al., 2011) lethal \| partially \| pupal stage (Wilson et al., 2006) viable (Wilson and Ashok, 1998) visible (Wilson et al., 2006)
Phenotype Manifest In
	eye (Wilson et al., 2006) lobula (Riddiford et al., 2010) lobula plate (Riddiford et al., 2010) optic lobe \| prepupal stage (Riddiford et al., 2010) ovary (Wilson et al., 2006) photoreceptor cell R7 \| prepupal stage (Riddiford et al., 2010) photoreceptor cell R8 \| prepupal stage (Riddiford et al., 2010) stage S8 oocyte (Wilson and Ashok, 1998) stage S9 oocyte (Wilson and Ashok, 1998) stage S10 oocyte (Wilson and Ashok, 1998) stage S11 oocyte (Wilson and Ashok, 1998) stage S12 oocyte (Wilson and Ashok, 1998) stage S13 oocyte (Wilson and Ashok, 1998) stage S14 oocyte (Wilson and Ashok, 1998)
Detailed Description
	Statement Reference Mutant larvae are resistant to the juvenile hormone agonist pyriproxyfen compared to wild type. Mutant females show reduced fecundity: they begin ovipositing at 6.0 days after eclosion (in contrast to 3.0 days for wild-type females) and after 30 days, the total number of eggs laid by a single mutant female is only 37% that of wild type. The hatching rate of the mutant eggs is only 78%. (Abdou et al., 2011) Mutant males treated with methoprene during larval development have normal appearing genitalia (wild-type control males show a failure of rotation of the genital disc under these conditions). (Baumann et al., 2010) Mutant prepupae show reduced proliferation in both the outer and the inner proliferation zones of the optic lobe at an early time compared to controls. In addition, they show precocious separation of the axons of photoreceptors R7 and R8 in the medulla which is evident by 6 hours after puparium formation. The mutants show a two-hour advancement in the ingrowth of lamina neurons into the medulla compared to controls. The gross anatomy of the lamina and medulla appears normal in mutant adults and there is no mistargeting of photoreceptor axons to inappropriate layers. However, the lobula shows gross abnormalities with irregular lobes that project towards, or sometimes penetrate, the medulla neuropil. These projections severely disrupt the layering of the lobula and the lobula plate, such that neurons that normally have their dendrites confined to a single layer now project in a disorganised fashion throughout the lobula. The beginnings of these irregular projections are evident at 12 hours after puparium formation. (Riddiford et al., 2010) Rst(1)JH²⁷ flies show good survival, with <15% mortality during pupal development. Rst(1)JH²⁷ females show only ~20% of the level of oogenesis seen in wild-type females. (Wilson et al., 2006) Homozygotes show increased resistance to methoprene compared to controls. Homozygous females have a reduced rate of oviposition compared to controls. 66% of mutant flies have a small number of defective ommatidia in the posterior quarter of the eye. (Wilson et al., 2006) Under normal conditions, 1 day old mutant females show a significantly lower juvenile hormone (JH)-hydrolysing activity compared to wild-type females. Mutant and wild-type females exposed to 38^oC show a significant decrease in JH-hydrolysing activity compared to control females at 25^oC. 1 day old mutant females have lower levels of stress reactivity (calculated as the percent decrease in JH-hydrolysing activity at 38^oC relative to normal conditions) than control females. Under normal conditions, the level of JH degradation in 5 day old mutant females is the same as in control females. After exposure to 38^oC, mature mutant female show no changes in the level of JH metabolism, in contrast to control females which show a significant decrease in JH-hydrolysing activity. (Gruntenko et al., 2000) Mutant females have significantly lower fertility than control flies at 25^oC. At 38^oC, control females show a much larger decrease in fertility compared to 25^oC than mutant females. (Gruntenko et al., 2000) Homozygous larvae show resistance to both the toxic and morphogenetic effects of methoprene compared to wild-type larvae. Heterozygous larvae show partial resistance to the morphogenetic effects of methoprene, but otherwise appear wild-type. Homozygous and hemizygous females show reduced oviposition; the onset of oviposition is delayed and the rate of oviposition is lower than wild-type. Homozygous females have fewer vitellogenic oocytes than wild-type females. (Wilson and Ashok, 1998)
External Data
Linkouts
Interactions
	Show the genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Statement Reference Met²⁷ has visible phenotype, enhanceable by br^rbp-2 (Wilson et al., 2006)
NOT Enhanced by
Statement Reference Met²⁷ has visible phenotype, non-enhanceable by br¹ (Wilson et al., 2006)
Suppressed by
Statement Reference Met²⁷ has chemical resistant phenotype, suppressible by gce^Scer\UAS.cBa/Scer\GAL4^Act5C.PI (Baumann et al., 2010) Met²⁷ has chemical resistant phenotype, suppressible by gce^Scer\UAS.cBa/Scer\GAL4^Lsp2.PH (Baumann et al., 2010) Met²⁷ has chemical resistant phenotype, suppressible by gce^Scer\UAS.cBa/Scer\GAL4^tub.PU (Baumann et al., 2010)
Enhancer of
Statement Reference Met²⁷/Rst(1)JH[+] is an enhancer of lethal phenotype of br^rbp-1 (Wilson et al., 2006) Met²⁷ is an enhancer of lethal phenotype of Scer\GAL4^tub.PU, gce^{dsRNA.Scer\UAS.cBa} (Baumann et al., 2010)
NOT Enhancer of
Statement Reference Met²⁷/Met²⁷ is a non-enhancer of lethal \| prepupal stage phenotype of br^2Bc-1 (Wilson et al., 2006, Wilson et al., 2006) Met²⁷/Met²⁷ is a non-enhancer of lethal \| prepupal stage phenotype of br⁵ (Wilson et al., 2006, Wilson et al., 2006)
Other
Statement Reference Met²⁷, br¹/br^2Bc-1 has viable phenotype (Wilson et al., 2006, Wilson et al., 2006, Wilson et al., 2006) Met²⁷, br¹ has lethal \| pharate adult stage phenotype (Wilson et al., 2006, Wilson et al., 2006) Met²⁷, br¹ has lethal phenotype (Wilson et al., 2006, Wilson et al., 2006, Wilson et al., 2006) Met²⁷, br⁵/br¹ has lethal \| prepupal stage phenotype (Wilson et al., 2006, Wilson et al., 2006, Wilson et al., 2006) Met²⁷, br⁵/br^2Bc-1 has lethal \| partially phenotype (Wilson et al., 2006, Wilson et al., 2006, Wilson et al., 2006) Met²⁷, br^rbp-1/br^2Bc-1 has lethal phenotype (Wilson et al., 2006, Wilson et al., 2006, Wilson et al., 2006) Met²⁷, br^rbp-1/br⁵ has lethal phenotype (Wilson et al., 2006, Wilson et al., 2006) Met²⁷, br^rbp-2/br^2Bc-1 has viable phenotype (Wilson et al., 2006, Wilson et al., 2006, Wilson et al., 2006) Met²⁷, br^rbp-2/br⁵ has lethal phenotype (Wilson et al., 2006, Wilson et al., 2006) Met²⁷, br^rbp-2/br^rbp-1 has lethal \| prepupal stage phenotype (Wilson et al., 2006, Wilson et al., 2006, Wilson et al., 2006) Met²⁷, br^rbp-2 has lethal \| pharate adult stage phenotype (Wilson et al., 2006, Wilson et al., 2006, Wilson et al., 2006) Met²⁷, gce^2.5k has developmental rate defective \| larval stage phenotype (Abdou et al., 2011) Met²⁷, gce^2.5k has increased cell death phenotype (Abdou et al., 2011) Met²⁷, gce^2.5k has lethal \| P-stage phenotype (Abdou et al., 2011) Met²⁷, gce^2.5k has small body \| larval stage phenotype (Abdou et al., 2011) Met²⁷, gce^2.5k has small body \| P-stage phenotype (Abdou et al., 2011) Met²⁷, Scer\GAL4^Act5C.PI, gce^{dsRNA.Scer\UAS.cBa} has lethal \| pupal stage phenotype (Baumann et al., 2010) Met²⁷, Scer\GAL4^tub.PU, gce^{dsRNA.Scer\UAS.cBa} has lethal \| pupal stage phenotype (Baumann et al., 2010) Met²⁷/Rst(1)JH[+], br^rbp-1 has lethal \| pupal stage phenotype (Wilson et al., 2006)
Phenotype Manifest In
Enhanced by
Statement Reference Met²⁷ has eye phenotype, enhanceable by br^rbp-2 (Wilson et al., 2006) Met²⁷ has ovary phenotype, enhanceable by br¹/br¹ (Wilson et al., 2006) Met²⁷ has ovary phenotype, enhanceable by br^rbp-2/br^rbp-2 (Wilson et al., 2006)
NOT Enhanced by
Statement Reference Met²⁷ has eye phenotype, non-enhanceable by br¹ (Wilson et al., 2006)
Enhancer of
Statement Reference Met²⁷/Met²⁷ is an enhancer of ovary phenotype of br¹ (Wilson et al., 2006, Wilson et al., 2006) Met²⁷/Met²⁷ is an enhancer of ovary phenotype of br^rbp-2 (Wilson et al., 2006, Wilson et al., 2006)
Other
Statement Reference Met²⁷, gce^2.5k has fat body phenotype (Abdou et al., 2011)
Additional Comments
Genetic Interactions
Statement Reference Onset of metamorphosis (larval wandering stage) is delayed approximately 12 hours compared to wild type in Met[27] gce[2.5k] double mutant larvae. Double mutant larvae and early pupae have a reduced body size compared to controls. The double mutants fail to undergo head eversion and die approximately 24 hours after pupariation. Fat body cells in the double mutants undergo precocious and enhanced programmed cell death compared to wild-type fat body cells. (Abdou et al., 2011) Expression of gce[Scer\UAS.cBa] under the control of either Scer\GAL4[Act5C.PI], Scer\GAL4[tub.PU] or Scer\GAL4[Lsp2.PH] reduces the increased resistance to methoprene which is seen in Met[27] animals. Met[27] males expressing gce[Scer\UAS.cBa] under the control of Scer\GAL4[tub.PU] and treated with methoprene during larval development show abnormal genital rotation (a response similar to wild-type males raised under these conditions). (Baumann et al., 2010) While 86% of br^rbp-2/br^rbp-2, Rst(1)JH²⁷/+ flies survive to adulthood, <2% of br^rbp-2/br^rbp-2, Rst(1)JH²⁷/Rst(1)JH²⁷ flies survive this far, with most dying during the pharate adult stage. br^rbp-1/br^rbp-1, Rst(1)JH²⁷/+ double mutants die at an earlier stage (prepupal/early pupal) than br^rbp-1/br^rbp-1 mutants. Expression of the Rst(1)JH^+tSt-H.hs transgene can rescue the lethality of br^rbp-2/br^rbp-2, Rst(1)JH²⁷/Rst(1)JH²⁷ or br^rbp-2/br^rbp-1, Rst(1)JH²⁷/Rst(1)JH²⁷ flies. br¹/br¹, Rst(1)JH²⁷/Rst(1)JH²⁷ mutants are lethal in both pupal and especially pharate adult stages, but small numbers of escaper adults eclose. When these mutants express the Rst(1)JH^+tSt-H.hs transgene, they survive to adulthood. Like br⁵ single mutants, br⁵, Rst(1)JH²⁷ double mutants are lethal in prepupal/early pupal development. 54% of br⁵/br¹, Rst(1)JH²⁷/+ mutants survive to adulthood but br⁵/br¹, Rst(1)JH²⁷/Rst(1)JH²⁷ mutants are lethal in prepupal/early pupal development. br¹/br¹, Rst(1)JH²⁷/Rst(1)JH²⁷ and br^rbp-2/br^rbp-2, Rst(1)JH²⁷/Rst(1)JH²⁷ female escapers show strong reductions in oogenesis. (Wilson et al., 2006) The expressivity of the defective eye phenotype seen in Met[27] flies is increased by br[rbp-2] but not by br[1]. (Wilson et al., 2006)
Xenogenetic Interactions
Statement Reference
Complementation & Rescue Data
Fails to complement	Met³ (Wilson and Ashok, 1998)
Rescued by	Met²⁷ is rescued by Met^+tSt-H.hs (Wilson and Ashok, 1998, Wilson et al., 2006)
Comments	The lethality of Met[27] gce[2.5k] double mutants is fully rescued by a single copy of Met[+t5.7] or by expression of gce[Scer\UAS.cBa] under the control of Scer\GAL4[arm.PS]. (Abdou et al., 2011) The defective eye phenotype seen in Met[27] flies is rescued by Met[+tSt-H.hs]. (Wilson et al., 2006)
Stocks ( 0 )

Notes on Origin
Discoverer

Comments
	Transformation of Rst(1)JH²⁷ mutants with a Rst(1)JH⁺ cDNA restores methoprene susceptibility. (Wilson et al., 1998)
External Crossreferences & Linkouts
Other Crossreferences

Linkouts

Synonyms & Secondary IDs ( 4 )
Reported As
Symbol Synonym	Met27 (Gruntenko et al., 1999) Met²⁷ (Wilson et al., 2006, Flatt and Kawecki, 2004, Wilson et al., 2002, Wilson et al., 2001, Pursley et al., 2000, Gruntenko et al., 2000, Gruntenko et al., 2000, Wilson et al., 1999, Wilson and Ashok, 1998, Wilson et al., 1998, Beno et al., 2005, Wilson et al., 2006, Baumann et al., 2010, Barry et al., 2008, Riddiford et al., 2010, Abdou et al., 2011) Rst(1)JH²⁷ Rst(1)JH^Met-27
Name Synonym
Secondary FlyBase IDs
	FBal0086770
References ( 18 )
Research paper	Abdou et al., 2011, Insect Biochem. Mol. Biol. 41(12): 938--945 Drosophila Met and Gce are partially redundant in transducing juvenile hormone action. [FBrf0216586] Baumann et al., 2010, Genetics 185(4): 1327--1336 Paralogous Genes Involved in Juvenile Hormone Action in Drosophila melanogaster. [FBrf0211496] Riddiford et al., 2010, Development 137(7): 1117--1126 A role for juvenile hormone in the prepupal development of Drosophila melanogaster. [FBrf0210225] Barry et al., 2008, Insect Biochem. Mol. Biol. 38(3): 346--353 Overexpression of Methoprene-tolerant, a Drosophila melanogaster gene that is critical for juvenile hormone action and insecticide resistance. [FBrf0202716] Wilson et al., 2006, Genetics 172(1): 253--264 Interaction between hormonal signaling pathways in Drosophila melanogaster as revealed by genetic interaction between Methoprene-tolerant and Broad-Complex. [FBrf0190778] Wilson et al., 2006, Mol. Genet. Genomics 276(3): 294--303 Wide mutational spectrum of a gene involved in hormone action and insecticide resistance in Drosophila melanogaster. [FBrf0193291] Flatt and Kawecki, 2004, Genetica 122(2): 141--160 Pleiotropic effects of methoprene-tolerant (Met), a gene involved in juvenile hormone metabolism, on life history traits in Drosophila melanogaster. [FBrf0180273] Gruntenko et al., 2000, J. Insect Physiol. 46(4): 451--456 Stress-reactivity of a Drosophila melanogaster strain with impaired juvenile hormone action. [FBrf0128480] Gruntenko et al., 2000, Insect Biochem. Mol. Biol.: 775--783 Stress-reactivity and juvenile hormone degradation in Drosophila melanogaster strains having stress-related mutations. [FBrf0128479] Pursley et al., 2000, Applebaum, Granger, 2000: 839--845 Intracellular localization and tissue specificity of the Methoprene-tolerant (Met) gene product in Drosophila melanogaster. [FBrf0128613] Gruntenko et al., 1999, D. I. S. 82: 7--8 Met, a mutation involved in juvenile hormone action, does not prevent changes in the hormone metabolism of Drosophila under stress. [FBrf0111891] Ashok et al., 1998, Proc. Natl. Acad. Sci. U.S.A. 95(6): 2761--2766 Insect juvenile hormone resistance gene homology with the bHLH-PAS family of transcriptional regulators. [FBrf0101869] Wilson and Ashok, 1998, Proc. Natl. Acad. Sci. U.S.A. 95(24): 14040--14044 Insecticide resistance resulting from an absence of target-site gene product. [FBrf0105957]
Abstract	Beno et al., 2005, Europ. Dros. Res. Conf. 19: SG8 Identification of molecular breakpoints in the alleles of Met gene mediating juvenile hormone action in Drosophila. [FBrf0184729] Wilson et al., 2002, A. Dros. Res. Conf. 43: 462C The Methoprene-tolerant gene mediates juvenile hormone action. [FBrf0145753] Wilson et al., 2001, A. Dros. Res. Conf. 42: 439A Involvement of the Methoprene-tolerant gene in juvenile hormone action. [FBrf0134040] Wilson et al., 1999, A. Dros. Res. Conf. 40: 141 Involvement of the Methoprene-tolerant gene in juvenile hormone action. [FBrf0107482] Wilson et al., 1998, A. Dros. Res. Conf. 39: 498C Juvenile hormone resistance gene Methoprene-tolerantis a bHLH-PAS family member. [FBrf0101535]

Allele Dmel\Met27

Allele Dmel\Met²⁷