Amino acid replacement: Q134term.
C8258685T
Q134term | mtg-PE; Q93term | mtg-PF
Q134term
Site of nucleotide substitution in mutant inferred by FlyBase based on reported amino acid change.
polysome & neuromuscular junction | embryonic stage (with Df(3R)CA3)
Homozygous embryonic neuromuscular junctions have strongly reduced glutamate-gated currents compared to wild type.
mtg1 and mtg1/Df(3R)CA3 mutant neuromuscular junctions show weak/limited glutamate-driven muscle contractions, with a 55% reduction in mean response amplitude.
mtg1 and mtg1/Df(3R)CA3 mutant neuromuscular junctions do not display defined excitatory junction currents (EJC) in over 70% of cases. Small and large isolated EJCs are observed in 14% of cases.
Homozygous embryos show a complete absence of movement and failure to hatch. Embryos manually removed from the eggcase show no movement and have a weakened cuticle that is typically accompanied by posterior gut herniation.
Mature embryos are completely paralysed, showing no spontaneous or touch-evoked movement, and show a 100% failure to hatch. The mutant embryos have a normal body anatomy, and a morphologically normal nervous system, musculature and neuromuscular junctions.
Mutant embryos that are manually hatched have a weakened cuticle and posterior gut herniation. A few of these embryos briefly show slight, uncoordinated movement in saline, but no indication of neurally induced body wall peristalsis.
mtg1/mtgP2 embryos show limited coordinated movement within the egg case, but they fail to hatch.
Homozygous and mtg1/Df(3R)CA3 mature embryos have a morphologically normal central nervous system and ventral nerve cord and normal peripheral axon extension, branching and targeting. Neuromuscular junction formation appears normal. Ultrastructurally at the neuromuscular junction, presynaptic bouton morphology and appearance, plasma membrane topology and electron-dense active zones with T-bars appear normal in homozygous and mtg1/Df(3R)CA3 embryos. There are no significant differences in mean bouton cross-sectional area, mitochondria size or number of synaptic vesicles clustered at the active zone between mutant and control animals. Mutant terminals show a significant increase (33% compared to wild type) in the incidence of plasma membrane cisternae structures and an increase in vesicles docked at the presynaptic membrane. The electron-dense matrix material (which is normally found restricted to the extracellular space between the pre- and post-synaptic membranes) is greatly reduced or absent in mtg1/Df(3R)CA3 mutants. This phenotype is specific to the cleft matrix domain as normal active zone T-bars are present presynaptically. Post-synaptic polyribosomes are reduced in number and density at more than 65% of the mutant synapses, and are instead often found in dispersed patches, in contrast to the tight packing found in wild-type post-synaptic domains.
Spontaneous excitatory junctional currents (EJCs) are the neuromuscular junction are largely silenced in homozygous and mtg1/Df(3R)CA3 embryos; occasional spontaneous EJCs are seen, but they display only small amplitudes and patterned bursts of large EJCs are not seen. Evoked transmission at the neuromuscular junction is also severely impaired; approximately 90% of nerve stimuli at homozygous and mtg1/Df(3R)CA3 neuromuscular junctions result in transmission failure, even with elevated stimulation frequencies, while evoked EJCs have reduced amplitudes (mean evoked amplitude is depressed by more than 90%) and more variable response latencies than at control neuromuscular junctions. Response to glutamate at the neuromuscular junction is reduced in homozygous embryos.
Animals expressing mtgdsRNA.Scer\UAS under the control of Scer\GAL4elav-C155 in a mtg1/+ background show reduced larval and adult viability, although substantial numbers of viable adults do survive.
mtg[+]/mtg1 is an enhancer of partially lethal - majority live | dominant phenotype of Neto109
The defective glutamate response of mtg1 embryos is not rescued by expression of GluRIIAScer\UAS.T:Hsap\MYC under the control of Scer\GAL4Mhc.PW.
mtg1 is partially rescued by mtgUAS.wt.EGFP/Scer\GAL4da.G32
mtg1 is partially rescued by Scer\GAL4da.G32/mtgΔCBD.UAS.EGFP
mtg1 is partially rescued by mtgC2-3.UAS.EGFP/Scer\GAL4da.G32
mtg1 is partially rescued by Scer\GAL4da.G32/mtgUAS.GFP
mtg1 is partially rescued by Scer\GAL4elav-C155/Scer\GAL4da.G32/mtgUAS.GFP
mtg1 is partially rescued by Scer\GAL4how-24B/mtgUAS.GFP
mtg1 is not rescued by Scer\GAL4elav-C155/mtgUAS.GFP
Expression of mtgScer\UAS.wt.T:Avic\GFP-EGFP under the control of Scer\GAL4da.G32 fully rescues the embryonic lethality of mtg1 homozygotes. Many of the rescued animals die later in development: 20% of the animals are fully rescued to adult viability, with fertile adult females. Glutamate-gated current amplitudes are restored to wild-type levels at the neuromuscular junctions of rescued embryos.
Expression of mtgΔCBD.Scer\UAS.T:Avic\GFP-EGFP under the control of Scer\GAL4da.G32 rescues movement in homozygous mtg1 embryos, although movement is weaker than normal and only a small number of embryos hatch. All larvae die almost immediately, either partially within the egg case, or after crawling and egg-length or two before arrest. Glutamate-gated current amplitudes are restored to wild-type levels at the neuromuscular junctions of rescued embryos.
Expression of mtgC2-3.Scer\UAS.T:Avic\GFP-EGFP under the control of Scer\GAL4da.G32 rescues limited embryonic movement and hatching in mtg1 homozygotes, although the larvae die shortly after hatching. Glutamate-gated current amplitudes are restored to wild-type levels at the neuromuscular junctions of rescued embryos.