mth1 mutant flies exhibit a statistically significant advantage in maintaining sustained flight over control flies at age 10 days, but not during middle and late life. At age 70 days, the trend reverses and parental control flies display a small advantage. The reversal point occurs at age 30 days and is maintained at every age category up to the oldest age tested. There is no pattern between the ability to maintain flight at 20 days and longevity. mth1 flies display a lower level of exploratory activity, relative to controls, particularly at ages 50 and 60 days.
Compared to controls, mth1 flies exposed to paraquat (to induce oxidative stress) show: i) less superoxide radical generation in the brain; ii) increased SOD activity in the brain; iii) less peroxynitrite generation in the brain; iv) lower lipid peroxidation in the brain; v) less degeneration of dopaminergic neurons; vi) lower alterations in DA and DOPAC levels; vii) lower levels of JNK signalling and cell death; viii) no improvement in the survival of dopaminergic neurons when co-exposed to the JNK inhibitor SP600125; ix) better locomotor behaviour in a climbing assay; and x) better age-related survival.
mth1 mutant larvae exposed to 2.0-5.0 μg/mL of endosulfan showed significantly higher survival rates compared to controls.
Mutant neuromuscular junctions show reliable homeostatic compensation (increase in quantal content) after treatment with philanthotoxin-433 for 10 minutes.
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.
Mutant flies show increased survival under hyperoxia (100% oxygen) compared to controls.
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/mthΔ6 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 1mMCa<up>2+</up>e, the quantal content is reduced to about half that of controls, and to about 40% in mth1/mthΔ6. 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.
Homozygous flies live on average 35% longer than control flies at both 25oC and 29oC. 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 36oC than control flies. Homozygous males and females weigh 20 to 30% more than control flies.
mth1/mthΔ6 is rescued by mthUAS.cSa/Scer\GAL4Toll-6-D42
mth1/mthΔ6 is rescued by mthUAS.cSa/Scer\GAL4hs.PB
mth1/mthΔ6 is not rescued by Scer\GAL4how-24B/mthUAS.cSa
Precise excision of the P{lacW} element reverts the life-span and stress resistance phenotypes of mth1.