Analogous deletion of K164 in human GOSR2 implicated in epilepsy, progressive myoclonic 6; mutation carried on in vitro construct; deletion coordinates in fly gene inferred by FlyBase curator based on reported deleted amino acid.
Membrin1524 homozygotes expressing MembrinK166del.Scer\UAS.T:Zzzz\FLAG under the control of Scer\GAL4da.G32 frequently die within the pupal case as fully developed pharate adults; when manually released from the pupal case, these adults appear weak and uncoordinated, as compared to controls. The respective third instar larvae also display a significantly decreased rate of locomotion, as compared to controls. The expression of MembrinK166del.Scer\UAS.T:Zzzz\FLAG alone under the control of either Scer\GAL4da.G32, Scer\GAL4nSyb.PS, Scer\GAL4elav.PU leads to a severe decrease in eclosion compared to controls.
The expression of MembrinK166del.Scer\UAS.T:Zzzz\FLAG alone under the control of Scer\GAL4da.G32 results in larval abdominal ddaC neurons exhibiting a severely reduced dendritic arborization, as shown by the significant decreases in dendritic length, number of terminal dendritic branches and dendritic intersections, but does not lead to any apparent defect in the growth and targeting of ppk-positive neurons (i.e. ddaC, vdaa, and vdaB neurons), as compared to controls.
Third instar larval neuromuscular junction expressing MembrinK166del.Scer\UAS.T:Zzzz\FLAG alone under the control of Scer\GAL4da.G32 exhibit presynaptic cytoskeleton defects, as shown by the fragmented pattern of the cytoskeletal protein Futsch and Ankyrin-2-XL, and exhibit synaptic boutons defects, as shown by significant increases in the numbers of retracted synaptic boutons, elongated synaptic boutons and boutons disconnected from the main axonal branch, but not in the overall bouton number or size, as compared to controls. This neuromuscular junctions also exhibit neurotransmission defects, as shown by a significant decrease in the frequency, but not amplitude or time course, of spontaneous miniature excitatory postsynaptic potentials, by the deformed trains of evoked excitatory postsynaptic potentials, and by the significant increase in the recovery time from electrically induced seizures, as compared to controls.
MembrinK166del.UAS.Tag:FLAG/Scer\GAL4da.G32 partially rescues Membrin1524
The expression of MembrinK166del.Scer\UAS.T:Zzzz\FLAG under the control of Scer\GAL4da.G32 improves the larval lethality of Membrin1524 homozygotes, allowing them to progress until the pharate stage.