Allele Dmel\mth¹

General Information
Symbol	Dmel\mth¹	Species	D. melanogaster
Name		FlyBase ID	FBal0094387
Feature type	allele	Associated gene	Dmel\mth
Also Known As	mth

Allele class	hypomorphic allele - molecular evidence, hypomorphic allele - genetic evidence
Mutagen	P-element activity
Recent Updates
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FB2013_03
FB2013_02
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Nature of the Allele
Allele class	hypomorphic allele - genetic evidence (Lin et al., 1998) hypomorphic allele - molecular evidence (Ja et al., 2009)
Mutagen	P-element activity (Lin 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
Caused by insertion	P{lacW}mth¹ (Lin et al., 1998, Song et al., 2002, Ja et al., 2009)
Cytology
Phenotypic Data
Phenotypic Class
	chemical resistant \| recessive (Lin et al., 1998) fertile (Lin et al., 1998) long lived \| recessive (Lin et al., 1998) neuroanatomy defective (Song et al., 2002) neurophysiology defective (Song et al., 2002) neurophysiology defective (with mth^Δ6) (Song et al., 2002) stress response defective (Walker and Benzer, 2004) viable (Lin et al., 1998) viable (with mth^Δ) (Ja et al., 2009)
Phenotype Manifest In
	male germline stem cell (Wallenfang et al., 2006) synapse (Song et al., 2002) synaptic vesicle (Song et al., 2002)
Detailed Description
	Statement Reference mth[1] mutant larvae exposed to 2.0-5.0 μg/mL of endosulfan showed significantly higher survival rates compared to controls. (Sharma et al., 2011) Mutant neuromuscular junctions show reliable homeostatic compensation (increase in quantal content) after treatment with philanthotoxin-433 for 10 minutes. (Dickman and Davis, 2009) Animals bearing mth[Δ] in trans to mth[1] are viable and show no obvious morphological or behavioural defects. Virgin female mth[Δ]/mth[1] mutants exhibit normal ovulation and mating frequencies after Acp70A injection. (Ja et al., 2009) Germline stem cells (GSCs) from newly eclosed mutant males show an S-phase index similar to wild-type. No decrease in S-phase index is seen in GSCs from mutant males that have been aged for 35 days, in contrast to wild-type aged controls. (Wallenfang et al., 2006) Mutant flies show increased survival under hyperoxia (100% oxygen) compared to controls. (Walker and Benzer, 2004) Mutants exhibit no gross morphological defects in the embryonic nervous system. In mth¹ homozygotes, the amplitudes of evoked excitatory junctional potentials (EJPs) are reduced to about 63% of those seen in controls. In mth¹/mth^Δ6 they reduced to about 57%. Electronic stimulation in the presence of 1uM Tetrodotoxin (TTX, a Na⁺ channel inhibitor) at a intensity of 2.5 fold over threshold abolishes nerve-evoked EJPs as also seen in wild-type. Stimulation with intensities 40-fold over threshold elicits saturated EJPs also as normal, however the electrotonic EJPs recorded from mutants are reduced to about half of control levels. The mean amplitude, the cumulative amplitude distribution, and the frequency of unitary mEJPs in mutant larvae show no significant differences from controls. The quantal content of evoked release in mutant neuromuscular junctions is equally reduced for all ^Ca<up>2+</up>_es. At 1mM^Ca<up>2+</up>_e, the quantal content is reduced to about half that of controls, and to about 40% in mth¹/mth^Δ6. Evoked excitatory junctional currents (EJCs) are reduced to about half of control amplitudes in mutants. Saturated extracellular EJPs are also significantly reduced to almost quarter of those in controls. Depolarisation-dependent Ca²⁺ entry and/or Ca²⁺ extrusion are normal in mutants. Calcimycin-induced release on mutants is significantly reduced to about half of control levels. The effect of latroinsectoxins on the frequency of mEJPs in mutants is indistinguishable from controls. The size of synaptic areas and the density of their associated vesicle populations are abnormal in mutant boutons. The mean synaptic area is reduced ro about 55% of controls. In addition the density of synaptic vesicles within 0-500 nm from the plasma membrane of a synaptic site is reduced to about a 2/3 of controls. The density of vesicles clustered around a synaptic site is also reduced. The density of vesicles within a distance of 0-50 nm and 50-300 nm from a synaptic area is reduced to about 3/4 and 2/3 of controls respectively. The density of vesicles located further away is not significantly reduced. During high frequency stimulation at 10Hz control EJPs depress within 3 s of stimulation to about 75% of their initial amplitude and are thereafter sustained, while in mutants, EJPs show neither an initial depression nor fatigue during the sustained period. Increasing the stimulation frequency to 30 Hz has no further effects on mutant amplitudes, while controls are depressed further. Phorbol 12-myristate 13-acetate (PMA) induced facilitation is absent in homozygous mutants at 0.5 mM ^Ca<up>2+</up>_e (as compared to wild-type where an increase in EJP amplitudes to ~238% of controls is seen). However at a ^Ca<up>2+</up>_e of 0.7 mM, PMA slightly facilitates evoked release in mutants. (Song et al., 2002) Homozygous flies live on average 35% longer than control flies at both 25^oC and 29^oC. Homozygous adults are more resistant to dietary paraquat, show a greater than 50% increase in average survival time in a starvation test and survive longer at 36^oC than control flies. Homozygous males and females weigh 20 to 30% more than control flies. (Lin et al., 1998)
External Data
Linkouts
Interactions
Phenotypic Class
Phenotype Manifest In
Additional Comments
Genetic Interactions
Statement Reference
Xenogenetic Interactions
Statement Reference
Complementation & Rescue Data
Complements	mth^Δ (Ja et al., 2009)
Rescued by	mth¹/mth^Δ6 is rescued by mth^Scer\UAS.cSa/Scer\GAL4^D42 (Song et al., 2002) mth¹/mth^Δ6 is rescued by mth^Scer\UAS.cSa/Scer\GAL4^hs.PB (Song et al., 2002)
Not rescued by	mth¹/mth^Δ6 is not rescued by Scer\GAL4^how-24B/mth^Scer\UAS.cSa/Scer\GAL4^how-24B (Song et al., 2002)
Comments	Animals bearing mth[Δ] in trans to mth[1] are viable and show no obvious morphological or behavioural defects. (Ja et al., 2009)
Stocks ( 1 )
Bloomington	27896 w^*; P{lacW}mth¹
Notes on Origin
Discoverer

Comments
	Precise excision of the P{lacW} element reverts the life-span and stress resistance phenotypes of mth¹. (Lin et al., 1998)
External Crossreferences & Linkouts
Other Crossreferences

Linkouts

Synonyms & Secondary IDs ( 2 )
Reported As
Symbol Synonym	mth (Walker and Benzer, 2004, Lin et al., 1998) mth¹ (Aravamudan and Broadie, 2003, Suh et al., 2008, Wallenfang et al., 2006, Sharma et al., 2011, Ja et al., 2009)
Name Synonym
Secondary FlyBase IDs

References ( 11 )
Research paper	Sharma et al., 2011, Chemosphere 82(3): 370--376 Transcriptome analysis provides insights for understanding the adverse effects of endosulfan in Drosophila melanogaster. [FBrf0212610] Dickman and Davis, 2009, Science 326(5956): 1127--1130 The schizophrenia susceptibility gene dysbindin controls synaptic homeostasis. [FBrf0209454] Ja et al., 2009, Protein Sci. 18(11): 2203--2208 The Drosophila G protein-coupled receptor, Methuselah, exhibits a promiscuous response to peptides. [FBrf0209193] Suh et al., 2008, PLoS ONE 3(5): e2152 An RGS-containing sorting nexin controls Drosophila lifespan. [FBrf0210283] Wallenfang et al., 2006, Aging Cell 5(4): 297--304 Dynamics of the male germline stem cell population during aging of Drosophila melanogaster. [FBrf0193116] Walker and Benzer, 2004, Proc. Natl. Acad. Sci. U.S.A. 101(28): 10290--10295 Mitochondrial 'swirls' induced by oxygen stress and in the Drosophila mutant hyperswirl. [FBrf0179503] Aravamudan and Broadie, 2003, J. Neurobiol. 54(3): 417--438 Synaptic Drosophila UNC-13 is regulated by antagonistic G-protein pathways via a proteasome-dependent degradation mechanism. [FBrf0155886] Song et al., 2002, Neuron 36(1): 105--119 Presynaptic regulation of neurotransmission in Drosophila by the G protein-coupled receptor Methuselah. [FBrf0152269] Toma et al., 2002, Nat. Genet. 31(4): 349--353 Identification of genes involved in Drosophila melanogaster geotaxis, a complex behavioral trait. [FBrf0152255] Lin et al., 1998, Science 282(5390): 943--946 Extended life-span and stress resistance in the Drosophila mutant methuselah. [FBrf0105270]
Abstract	Song et al., 2001, Bellen, Taylor, 2001: 251 Methuselah, a putative G protein-coupled receptor, regulates excitatory neurotransmitter exocytosis at the larval neuromuscular junction of Drosophila. [FBrf0144681]

Allele Dmel\mth1

Allele Dmel\mth¹