ElavGAL4/UAS-htorsinAΔE males exhibited a severe locomotion deficit, approaching that of the dtorsin-null mutant (26.7±3.4, n = 9, p<0.0001) (Fig. 1A, column 4, compared to column 2).
Male larvae co-expressing DtorsinΔE and wild type Dtorsin also exhibited a locomotion deficit (38.54±2.8, n = 15, p = 0.0012) (Fig. 5, column 4 compared to column 1) similar to the deficit caused by expression of DtorsinΔE only (column 3).
While pan-neuronal expression of human wild type torsinA could rescue the locomotion deficit phenotype of dtorsin KO13 males (Fig. 1A, columns 6,7), human torsinAΔE was unable to do so (20.5±2.0, n = 21) (Fig. 1A, column 8).
Similarly, mutant males co-expressing DtorsinΔE and wild type Dtorsin transgenes exhibited a locomotion deficit that was not significantly different from that of the dtorsin KO13 larvae (UAS- dtorsin(A11) and UAS- dtorsinΔE(#12); 32.4±4.2, n = 7, not significant) (Fig. 5, column 11); UAS -dtorsin(B5) and UAS- dtorsinΔE(#21): 29.9±3.6, n = 14, not significant) (Fig. 5, column 12).
In striking contrast to the rescuing effect of wild type Dtorsin expression, DtorsinΔE expression in male dtorsin KO13 larvae failed to rescue the locomotion deficit (22.9±2.8, n = 13, not significant) with a slight reduction of peristaltic rate (Fig. 5, column 9), relative to dtorsin KO13 males (Fig. 5, column 5).
Although pan-neuronal expression of wild type Dtorsin did not affect larval locomotion in wild type Drosophila (peristaltic frequency 53.0±1.5, n = 8, not significant) (Fig. 5, column 2) compared to wild type (53.0±1.8, n = 9) (Fig. 5, column 1), wild type male larvae expressing DtorsinΔE exhibited a significant locomotion deficit (38.7±2.5, n = 23, p = 0.002) (Fig. 5, column 3).
Ma, L. et al. Human embryonic stem cell-derived gaba neurons correct locomotion deficits in quinolinic acid-lesioned mice.
Animals with defects in Eaat1 (GLAST), which takes up glutamate, or Gat, which in turn takes up GABA, show severe locomotion deficits and animals hardly move.
While panglial knockdown of shopper (see Fig. 1h) causes characteristic locomotion deficits (three independent RNAi strains leading to similar results), no abnormal phenotypes are detected upon silencing of shopper in neurons (see below).
The total distance traveled by WT and KO mice were also very similar underscoring the lack of locomotion deficits in αB-crystallin/HspB2 knockout mice at this age.
The mice were weighed and visually inspected weekly, and were scored for gross morphological and motor abnormalities including the onset of kyphosis, abnormalities in hind limb extension when lifted by the tail, and balance and locomotion deficits.
