Pan-neuronal expression of Mmus\Prnp^{Scer\UAS.T:Hsap\PRNP-3F4} under the control of Scer\GAL4^elav-C155 results in functional changes in the NMJ. There is an increase in mean miniature excitatory junctional current (mEJC) amplitude compared with wild type, but to a lesser extent than with Mmus\Prnp^{Scer\UAS.T:Hsap\PRNP-3F4}. Mean synaptic vesicle size is increased compared to controls in both type 1s and 1b boutons. Evoked EJC amplitudes at low frequency stimulation are not enhanced upon expression of Mmus\Prnp^{Scer\UAS.T:Hsap\PRNP-3F4}. There is a decrease in the size of the ready release pool of vesicles, but the initial release probability is similar to controls. No morphological changes are observed in the NMJs: they are a similar size and contain a similar amount of brp+ active zones as controls.

Expression of Mmus\Prnp^{P101L.Scer\UAS} under the control of Scer\GAL4^elav-C155 causes an increase in larval locomotor activity compared to controls, as detected in greater crawling distances.

Scer\GAL4^Cha.7.4-mediated expression of Mmus\Prnp^{P101L.Scer\UAS} causes some third instar larvae to crawl backwards along the sides of their vials and often stop to swing the anterior parts of their bodies. These larvae also burrow through the culture media to the bottom of the vial, where they often died.

Approximately 50% of Scer\GAL4^Cha.7.4 Mmus\Prnp^{P101L.Scer\UAS} animals eclose.

Approximately 68% of Scer\GAL4^Ddc.PL Mmus\Prnp^{P101L.Scer\UAS} animals eclose.

The majority (5/6) of Scer\GAL4^Cha.7.4 Mmus\Prnp^{P101L.Scer\UAS} third instar larval brains display no obvious neuropathology.

Newly eclosed flies expressing Mmus\Prnp^{P101L.Scer\UAS} under the control of Scer\GAL4^Cha.7.4 exhibit severe locomotor dysfunction: they do not fly, walk slowly, have difficulty righting themselves when knocked over, and excessively groom their wings and antennae. In a climbing assay, 82-94% of these flies do not climb and often remain motionless.

Newly eclosed flies expressing Mmus\Prnp^{P101L.Scer\UAS} under the control of Scer\GAL4^Ddc.PLdisplay mild coordination defects in that their legs often move in an uncontrolled, flailing motion. However, these flies do not perform statistically worse than controls in a climbing assay.

The majority of eclosed Scer\GAL4^Cha.7.4 Mmus\Prnp^{P101L.Scer\UAS} flies die by 3-4 weeks, compared to 8-10 weeks for controls, representing a ~50% reduction in lifespan.

20-90% of eclosed Scer\GAL4^Ddc.PL Mmus\Prnp^{P101L.Scer\UAS} flies are dead within 24hr post-eclosion.

The adult brains of Scer\GAL4^Cha.7.4 Mmus\Prnp^{P101L.Scer\UAS} files are histologically normal at 1d of age, but by day 14-28, these flies show numerous neuropil vacuoles in their brains, particularly in the optic lobes. Apoptosis is not increased in these brains.