Overexpression of Hsap\TARDBP^{A315T.Scer\UAS.T:Avic\GFP-YFP} driven in the adult retina by Scer\GAL4^GMR.PU causes a neurodegeneration phenotype, with visible depigmentation.

Expression of Hsap\TARDBP^{A315T.Scer\UAS.T:Avic\GFP-YFP} in motor neurons under the control of Scer\GAL4^D42 results in nuclear morphology defects and smaller synapses compared with wild-type. This anatomical phenotype is accompanied by an impairment in locomotor function, as indicated by a significant increase in larval turning time compared with controls.

Compared with controls, expression of Hsap\TARDBP^{A315T.Scer\UAS.T:Avic\GFP-YFP} in glial cells under the control of Scer\GAL4^repo.PU results in significantly smaller neuromuscular junctions (NMJs) with a decreased number of synaptic boutons. When tested for their ability to turn, larvae expressing the transgene in glia also exhibit a significant impairment in locomotor function.

Hsap\TARDBP^{A315T.Scer\UAS.T:Avic\GFP-YFP}-expression leads to a mismatch of pre- and post-synaptic areas. Expression of Hsap\TARDBP^{A315T.Scer\UAS.T:Avic\GFP-YFP} in motor neurons leads to a significant increase in the area of pre-synaptic active zones, while its expression in glia results in reduction in the size of post-synaptic areas.

Both motor neuron and glial expression of Hsap\TARDBP^{A315T.Scer\UAS.T:Avic\GFP-YFP} can lead to alterations in adult locomotion and sleep patterns.

Expression of Hsap\TARDBP^{A315T.Scer\UAS.T:Avic\GFP-YFP} in the eye under the control of Scer\GAL4^GMR.PF has no visible phenotype in the 1-2 day old adult eye at 25[o]C, although cell loss and neurodegeneration can be seen in retinal sections. Visible loss of pigmentation is seen by 5 days old and worsens with age. When the temperature is increased to 29[o]C visible retinal neurodegeneration can be seen at 1-3 days.

Expression of Hsap\TARDBP^{A315T.Scer\UAS.T:Avic\GFP-YFP} under the control of Scer\GAL4^D42 has no effect on the number of boutons in the larval neuromuscular junction when the transgene is expressed at comparable levels to Hsap\TARDBP^{Scer\UAS.T:Avic\GFP-YFP.cEa}. The number of synaptic vesicles, satellite boutons and axonal branches are also similar to wild type. However the phenotype is dosage dependent, with phenotypes seen when Hsap\TARDBP^{A315T.Scer\UAS.T:Avic\GFP-YFP} is expressed at higher levels. A decreased number of boutons is seen in the larval neuromuscular junction and the number of synaptic vesicles is also reduced compared to wild type. Supernumerary satellite boutons are present but the number of axonal branches is similar to wild type.

Expression of Hsap\TARDBP^{A315T.Scer\UAS.T:Avic\GFP-YFP} under the control of Scer\GAL4^D42 results in locomotor defects in third instar larvae. Crawling larvae rolled ventral side up take longer to turn back to dorsal side up. The higher the expression the more severe the phenotype.

Flies expressing Hsap\TARDBP^{A315T.Scer\UAS.T:Avic\GFP-YFP} under the control of Scer\GAL4^D42 are viable (when expressed at comparable levels to Hsap\TARDBP^{Scer\UAS.T:Avic\GFP-YFP.cEa}. Higher levels of expression results in pupal lethality.

48% of flies expressing Hsap\TARDBP^{Scer\UAS.T:Avic\GFP-YFP.cEa} under the control of Scer\GAL4^D42 fail to live to 30 days at 18[o]C, compared to 30% of controls. 98% of flies die by 30 days at 25[o]C.

Flies expressing Hsap\TARDBP^{A315T.Scer\UAS.T:Avic\GFP-YFP} under the control of Scer\GAL4^D42 are unable to climb at 18[o]C at 30 days old. No significant difference is seen from controls at two days old. A progressive decline in climbing ability is seen at 25[o]C.

Expression of Hsap\TARDBP^{A315T.Scer\UAS.T:Avic\GFP-YFP} under the control of Scer\GAL4^D42 at at comparable levels to Hsap\TARDBP^{Scer\UAS.T:Avic\GFP-YFP.cEa} does not result in motor neuron apoptosis in the larval ventral ganglia. Some apoptosis is seen at higher expression levels but mutants die as pupae.

A small amount of motor neuron loss is seen in the adult thoracic ganglion of flies expressing Hsap\TARDBP^{A315T.Scer\UAS.T:Avic\GFP-YFP} under the control of Scer\GAL4^D42.

Hsap\TARDBP^{A315T.UAS.YFP}, Scer\GAL4^GMR.PU has visible phenotype, enhanceable by Pabp2⁵⁵

Hsap\TARDBP^{A315T.UAS.YFP}, Scer\GAL4^GMR.PU has abnormal neuroanatomy | adult stage phenotype, enhanceable by Pabp2⁵⁵

Hsap\TARDBP^{A315T.UAS.YFP}, Scer\GAL4^GMR.PF has visible | adult stage phenotype, enhanceable by Prosβ2^1.UAS, Scer\GAL4^GMR.PF

Hsap\TARDBP^{A315T.UAS.YFP}, Scer\GAL4^Toll-6-D42 has abnormal locomotor behavior | third instar larval stage phenotype, enhanceable by TBPH^GD6943, Scer\GAL4^Toll-6-D42

Hsap\TARDBP^{A315T.UAS.YFP}, Scer\GAL4^GMR.PF has visible | adult stage phenotype, suppressible | partially by Hsap\HSPA1L^UAS.cWa, Scer\GAL4^GMR.PF

Hsap\TARDBP^{A315T.UAS.YFP}, Scer\GAL4^GMR.PF has visible | adult stage phenotype, suppressible | partially by BacA\p35^UAS.cHa, Scer\GAL4^GMR.PF

Hsap\TARDBP^{A315T.UAS.YFP}, Scer\GAL4^GMR.PU has eye phenotype, enhanceable by Pabp2⁵⁵

Hsap\TARDBP^{A315T.UAS.YFP}, Scer\GAL4^GMR.PF has eye | heat sensitive phenotype, enhanceable by Prosβ2^1.UAS, Scer\GAL4^GMR.PF

Hsap\TARDBP^{A315T.UAS.YFP}, Scer\GAL4^GMR.PF has eye | heat sensitive phenotype, suppressible | partially by Hsap\HSPA1L^UAS.cWa, Scer\GAL4^GMR.PF

Hsap\TARDBP^{A315T.UAS.YFP}, Scer\GAL4^GMR.PF has eye | heat sensitive phenotype, suppressible | partially by BacA\p35^UAS.cHa, Scer\GAL4^GMR.PF