Amino acid replacement: P58S.
C3951522T
P58S | Vap33-PA; P58S | Vap33-PB; P58S | Vap33-PE; P58S | Vap33-PC
P58S
Analogous mutation in human VAPB implicated in amyotrophic lateral sclerosis 8 and spinal muscular atrophy, late onset, Finkel type; mutation carried on in vitro construct; site of nucleotide substitution in fly gene inferred by FlyBase curator.
Transgenic larvae expressing Vap-33-1P58S.Scer\UAS in neurons (under the control of Scer\GAL4elav-C155) are sluggish and uncoordinated.
Transgenic larvae expressing Vap-33-1P58S.Scer\UAS in neurons (under the control of Scer\GAL4elav-C155) reveal significant heterogeniety in mobility. Approximately 34% of the larvae are completely paralyzed or exhibit very few peristaltic contractions while the majority has a frequency of strides that is only 30% of the wild-type value. Significantly enhanced neuronal death is observed in the central neurons of larvae expressing Vap-33-1P58S.Scer\UAS compared with controls.
The number of boutons in neuromuscular junctions expressing Vap-33-1P58S.Scer\UAS (under the control of Scer\GAL4elav-C155) is approximately 40% of the wild-type number. Although not directly quantified, an increase in bouton size is also observed. A number of other abnormalities such as muscle wasting and synaptic degeneration are often observed at these NMJs.
TEM analysis of wing disc cells expressing Vap-33-1Scer\UAS.cPa under the control of Scer\GAL4C5 reveals clusters of aberrant electron-dense material that is continuous with the rough ER. These clusters are not seen in wild type controls.
Pre-synaptic expression of Vap-33-1Scer\UAS.cPa under the control of Scer\GAL4elav-C155 has no effect on bouton number. Mild defects in flight ability are observed but no defects are detected in the structure of the indirect flight muscles. Subtle but non-significant reductions in the excitatory junctional amplitude (EJP) and (miniEJP) are also seen.