Table 6.
Detailed results and statistical analyses related to motor functions
| Gait analysis | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Genotype | Cohort | Genotype ×cohort | Pairwisecomparisons | ||||||||||||||
| Test | Datastructure | WT | Het | KO | F | pvalue | Power | F | pvalue | Power | F | pvalue | Power | WT vsHet | WT vsKO | Het vs KO | |
| Stance mean (cm) | 2wANOVA | Normal | 3.55 ± 0.09 | 3.41 ± 0.12 | 3.27 ± 0.14 | 1.466 | 0.240 | 0.299 | 40.902 | 0.000 | 1.000 | 1.291 | 0.284 | 0.267 | − | − | − |
| Stance variance (cm) | 2wANOVA | Nonnormal | 0.15 ± 0.04 | 0.15 ± 0.03 | 0.17 ± 0.05 | 0.189 | 0.829 | 0.078 | 14.972 | 0.000 | 0.967 | 0.735 | 0.484 | 0.168 | − | − | − |
| Stride mean (cm) | 2wANOVA | Normal | 5.39 ± 0.23 | 5.64 ± 0.21 | 6.43 ± 0.24 | 5.443 | 0.007 | 0.826 | 15.476 | 0.000 | 0.971 | 0.499 | 0.610 | 0.127 | 0.674 | 0.003 | 0.028 |
| Stride variance (cm) | 2wANOVA | Nonnormal | 0.77 ± 0.13 | 0.86 ± 0.14 | 0.83 ± 0.18 | 0.137 | 0.873 | 0.070 | 12.150 | 0.001 | 0.928 | 3.459 | 0.039 | 0.622 | − | − | − |
| Sway mean (cm) | 2wANOVA | Nonnormal | 3.4 ± 0.17 | 3.55 ± 0.16 | 3.59 ± 0.22 | 0.191 | 0.826 | 0.078 | 186.368 | 0.000 | 1.000 | 2.443 | 0.097 | 0.470 | − | − | − |
| Sway variance (cm) | 2wANOVA | Nonnormal | 0.08 ± 0.01 | 0.17 ± 0.04 | 0.14 ± 0.02 | 1.909 | 0.159 | 0.378 | 3.781 | 0.057 | 0.479 | 0.400 | 0.672 | 0.111 | − | − | − |
| Open field spontaneous activity (traveled distance) | |||||||||||||||||
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Test | Data structure | WT | Het | KO | F | p value | Power | F | p value | Power | F | p value | Power | WT vs Het | WT vs KO | Het vsKO | |
| Total distance (cm) | 2wANOVA | Normal | 13,816.17 ± 828.27 | 11,273.16 ± 764.09 | 10,099.24 ± 621.43 | 6.633 | 0.003 | 0.896 | 12.836 | 0.001 | 0.940 | 0.073 | 0.930 | 0.061 | 0.016 | 0.001 | 0.299 |
| Distance | Test | Data structure | F | p value | Power | WT vs Het | WT vs KO | Het vsKO | |||||||||
| - Time | rMeasures | Sph.viol | 36.350 | 0.000 | 1.000 | − | − | − | |||||||||
| - Time × gen. | rMeasures | Sph.viol | 2.235 | 0.029 | 0.917 | − | − | − | |||||||||
| - Genotype | rMeasures | Sph.viol | 6.633 | 0.003 | 0.896 | 0.029 | 0.001 | 0.449 | |||||||||
| - Cohort | rMeasures | Sph.viol | 12.836 | 0.001 | 0.940 | − | − | − | |||||||||
| - Time × gen. × coh. | rMeasures | Sph.viol | 0.878 | 0.532 | 0.461 | − | − | − | |||||||||
| - gen. × coh. | rMeasures | Sph.viol | 0.073 | 0.930 | 0.061 | − | − | − | |||||||||
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Individual time bins | Test | Data structure | WT | Het | KO | F | p value | Power | F | p value | Power | F | p value | Power | WT vs Het | WT vs KO | Het vsKO |
| Distance 0-10 min | 2wANOVA | Normal | 2723.06 ± 185.28 | 2365.11 ± 166.4 | 2479.64 ± 164.36 | 0.894 | 0.415 | 0.196 | 7.573 | 0.008 | 0.770 | 0.224 | 0.800 | 0.083 | − | − | − |
| Distance 10-20 min | 2wANOVA | Nonnormal | 2516.77 ± 150.09 | 2064.33 ± 169.75 | 1684.88 ± 108.32 | 8.357 | 0.001 | 0.954 | 13.148 | 0.001 | 0.945 | 0.026 | 0.975 | 0.054 | 0.030 | 0.000 | 0.069 |
| Distance 20-30 min | 2wANOVA | Normal | 2349.52 ± 168.15 | 1919.27 ± 159.57 | 1466.99 ± 150.82 | 7.936 | 0.001 | 0.943 | 11.962 | 0.001 | 0.924 | 0.362 | 0.698 | 0.105 | 0.051 | 0.000 | 0.051 |
| Distance 30-40 min | 2wANOVA | Normal | 2203.27 ± 139.79 | 1680.09 ± 143.29 | 1589.41 ± 114.03 | 6.091 | 0.004 | 0.868 | 11.521 | 0.001 | 0.915 | 0.020 | 0.980 | 0.053 | 0.007 | 0.002 | 0.710 |
| Distance 40-50 min | 2wANOVA | Normal | 2090.38 ± 156.71 | 1657.47 ± 139.76 | 1380 ± 116.11 | 6.255 | 0.004 | 0.877 | 5.904 | 0.019 | 0.664 | 0.035 | 0.965 | 0.055 | 0.035 | 0.001 | 0.185 |
| Distance 50-60 min | 2wANOVA | Nonnormal | 1933.14 ± 160.59 | 1586.87 ± 98.6 | 1498.28 ± 139.38 | 3.074 | 0.055 | 0.568 | 3.755 | 0.058 | 0.477 | 1.459 | 0.242 | 0.298 | 0.055 | 0.026 | 0.733 |
| Rotarod | |||||||||||||||||
| Latency | Test | Data structure | F | p value | Power | WT vs Het | WT vs KO | Het vsKO | |||||||||
| - Trial | rMeasures | Sph.viol | 9.369 | 0.000 | 1.000 | − | − | − | |||||||||
| - Trial × gen. | rMeasures | Sph.viol | 2.268 | 0.015 | 0.921 | − | − | − | |||||||||
| - Genotype | rMeasures | Sph.viol | 8.888 | 0.000 | 0.964 | 0.123 | 0.000 | 0.044 | |||||||||
| - Cohort | rMeasures | Sph.viol | 2.573 | 0.115 | 0.350 | − | − | − | |||||||||
| - Session × gen. × coh. | rMeasures | Sph.viol | 1.867 | 0.050 | 0.848 | − | − | − | |||||||||
| - Gen. × coh. | rMeasures | Sph.viol | 0.726 | 0.489 | 0.166 | − | − | − | |||||||||
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Individual trials | Test | Data structure | WT | Het | KO | F | pvalue | Power | F | pvalue | Power | F | pvalue | Power | WT vs Het | WT vs KO | Het vsKO |
| Latency trial 1 | 2wANOVA | Normal | 181.28 ± 15.25 | 175.51 ± 14.58 | 149.17 ± 13.24 | 1.323 | 0.275 | 0.273 | 0.053 | 0.819 | 0.056 | 1.320 | 0.276 | 0.273 | − | − | − |
| Latency trial 2 | 2wANOVA | Normal | 198.66 ± 19.58 | 190.76 ± 20.22 | 135.84 ± 15.82 | 3.395 | 0.041 | 0.614 | 0.001 | 0.979 | 0.050 | 3.956 | 0.025 | 0.685 | 0.947 | 0.042 | 0.085 |
| Latency trial 3 | 2wANOVA | Normal | 222.75 ± 20.99 | 178.3 ± 14.43 | 128.94 ± 14.01 | 7.010 | 0.002 | 0.913 | 1.047 | 0.311 | 0.171 | 0.816 | 0.448 | 0.182 | 0.159 | 0.001 | 0.106 |
| Latency trial 4 | 2wANOVA | Normal | 260.92 ± 18.73 | 209.71 ± 15.54 | 168.01 ± 16.99 | 6.767 | 0.002 | 0.902 | 3.832 | 0.056 | 0.484 | 0.017 | 0.983 | 0.052 | 0.094 | 0.001 | 0.203 |
| Latency trial 5 | 2wANOVA | Normal | 270.8 ± 21.62 | 228.95 ± 22.25 | 172.55 ± 21.59 | 4.498 | 0.016 | 0.744 | 1.536 | 0.221 | 0.229 | 1.050 | 0.357 | 0.224 | 0.368 | 0.007 | 0.168 |
| Latency trial 6 | 2wANOVA | Normal | 273.51 ± 19.16 | 192.29 ± 25.69 | 133.8 ± 15.59 | 11.838 | 0.000 | 0.992 | 9.021 | 0.004 | 0.838 | 0.222 | 0.802 | 0.083 | 0.013 | 0.000 | 0.094 |
| Latency day 1 | 2wANOVA | Normal | 200.9 ± 15.13 | 181.52 ± 14.32 | 137.98 ± 11.9 | 5.026 | 0.010 | 0.793 | 0.108 | 0.744 | 0.062 | 2.253 | 0.115 | 0.438 | 0.578 | 0.006 | 0.072 |
| Latency day 2 | 2wANOVA | Normal | 268.41 ± 16.68 | 210.32 ± 19.07 | 158.12 ± 14.54 | 10.061 | 0.000 | 0.980 | 5.783 | 0.020 | 0.655 | 0.060 | 0.942 | 0.059 | 0.041 | 0.000 | 0.073 |
| Beam walking | |||||||||||||||||
| Genotype | Cohort | Genotype × cohort | Pairwisecomparisons | ||||||||||||||
| Test | Data structure | WT | Het | KO | F | p value | Power | F | p value | Power | F | p value | Power | WT vs Het | WT vs KO | Het vsKO | |
| % mice falling (large) | 2wANOVA | NA | 0 ± 0 | 0 ± 0 | 0 ± 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | − | − | − |
| % mice falling (medium) | 2wANOVA | Nonnormal | 0 ± 0 | 0 ± 0 | 6.57 ± 2.59 | 6.339 | 0.003 | 0.882 | 0.395 | 0.533 | 0.095 | 0.396 | 0.675 | 0.111 | 1.000 | 0.003 | 0.003 |
| % mice falling (small) | 2wANOVA | Nonnormal | 32.89 ± 7.41 | 26.31 ± 7.27 | 78.94 ± 6.12 | 16.788 | 0.000 | 1.000 | 3.622 | 0.063 | 0.463 | 0.972 | 0.385 | 0.210 | 0.366 | 0.000 | 0.000 |
| Distance (large,cm) | 2wANOVA | Nonnormal | 95.05 ± 2.27 | 90.92 ± 4.66 | 99.07 ± 0.92 | 1.819 | 0.173 | 0.362 | 1.416 | 0.240 | 0.215 | 0.242 | 0.786 | 0.086 | − | − | − |
| Distance (medium, cm) | 2wANOVA | Nonnormal | 87.17 ± 4.25 | 90.41 ± 4.35 | 88.15 ± 5.03 | 0.129 | 0.879 | 0.069 | 2.525 | 0.118 | 0.344 | 0.482 | 0.620 | 0.125 | − | − | − |
| Distance (small, cm) | 2wANOVA | Normal | 47.19 ± 5.45 | 53.77 ± 8.03 | 26.24 ± 6.14 | 4.380 | 0.018 | 0.732 | 0.447 | 0.507 | 0.101 | 0.346 | 0.709 | 0.102 | 0.438 | 0.044 | 0.006 |
| % mice fully crossing (large) | 2wANOVA | Nonnormal | 94.73 ± 2.4 | 89.47 ± 5.83 | 98.68 ± 1.31 | 1.567 | 0.219 | 0.317 | 1.486 | 0.228 | 0.223 | 0.107 | 0.899 | 0.066 | − | − | − |
| % mice fully crossing (medium) | 2wANOVA | Nonnormal | 76.31 ± 7.01 | 80.7 ± 7.12 | 80.26 ± 7.29 | 0.089 | 0.915 | 0.063 | 4.278 | 0.044 | 0.528 | 0.947 | 0.394 | 0.205 | − | − | − |
| % mice fully crossing (small) | 2wANOVA | Nonnormal | 27.63 ± 7.12 | 38.4 ± 9.57 | 9.21 ± 5.47 | 3.568 | 0.035 | 0.637 | 0.692 | 0.409 | 0.129 | 0.316 | 0.730 | 0.098 | 0.278 | 0.128 | 0.010 |
| Paw misplacements (large, all mice) | 2wANOVA | Nonnormal | 0.47 ± 0.14 | 0.56 ± 0.16 | 1.06 ± 0.14 | 4.197 | 0.021 | 0.712 | 0.137 | 0.713 | 0.065 | 1.662 | 0.200 | 0.334 | 0.693 | 0.010 | 0.026 |
| Paw misplacements (medium, all mice) | 2wANOVA | Normal | 1.71 ± 0.29 | 1.5 ± 0.26 | 2.38 ± 0.41 | 1.762 | 0.182 | 0.352 | 0.525 | 0.472 | 0.110 | 0.055 | 0.947 | 0.058 | − | − | - |
| Paw misplacements (small, all mice) | 2wANOVA | Nonnormal | 1.44 ± 0.13 | 2.48 ± 0.47 | 1.78 ± 0.18 | 3.330 | 0.044 | 0.605 | 3.700 | 0.060 | 0.471 | 0.760 | 0.473 | 0.172 | 0.015 | 0.462 | 0.082 |
| Paw misplacements (large, crossing mice) | 2wANOVA | Nonnormal | 0.52 ± 0.17 | 0.6 ± 0.17 | 1.07 ± 0.14 | 3.194 | 0.049 | 0.585 | 0.210 | 0.649 | 0.073 | 1.333 | 0.273 | 0.275 | 0.937 | 0.053 | 0.119 |
| Paw misplacements (medium, crossing mice) | 2wANOVA | Nonnormal | 1.67 ± 0.33 | 1.37 ± 0.27 | 2.33 ± 0.53 | 1.343 | 0.271 | 0.276 | 0.851 | 0.361 | 0.148 | 0.027 | 0.973 | 0.054 | − | − | − |
| Paw misplacements (small, crossing mice) | 2wANOVA | Nonnormal | 1.79 ± 0.23 | 2.77 ± 0.53 | 2.81 ± 0.64 | 1.189 | 0.327 | 0.227 | 2.465 | 0.134 | 0.318 | 0.102 | 0.904 | 0.063 | − | − | − |
| Time to cross (large, fully crossing) | 2wANOVA | Nonnormal | 10.05 ± 1.3 | 9.11 ± 1.91 | 7.17 ± 1.15 | 0.911 | 0.409 | 0.199 | 3.043 | 0.087 | 0.402 | 1.213 | 0.306 | 0.253 | − | − | − |
| Time to cross (medium, fully crossing) | 2wANOVA | Nonnormal | 28.54 ± 5.32 | 16.62 ± 3.28 | 18.14 ± 4.47 | 1.643 | 0.204 | 0.330 | 2.898 | 0.095 | 0.386 | 2.415 | 0.100 | 0.464 | − | − | − |
| Time to cross (small, fully crossing) | 2wANOVA | Normal | 54.56 ± 7.16 | 44.74 ± 5.25 | 22.43 ± 6 | 4.119 | 0.030 | 0.667 | 0.037 | 0.850 | 0.054 | 2.660 | 0.092 | 0.473 | 0.479 | 0.030 | 0.169 |
| Time to cross (large, all mice) | 2wANOVA | Nonnormal | 15.75 ± 3.07 | 20.75 ± 6.73 | 8.5 ± 2.21 | 4.443 | 0.027 | 0.370 | 0.327 | 0.574 | 0.094 | 0.427 | 0.659 | 0.070 | 0.015 | 0.033 | 0.820 |
| Time to cross (medium, all mice) | 2wANOVA | Nonnormal | 46.34 ± 8.74 | 36.11 ± 8.58 | 34.61 ± 8.93 | 1.157 | 0.337 | 0.109 | 1.444 | 0.245 | 0.682 | 0.472 | 0.632 | 0.218 | − | − | − |
| Time to cross (small, all mice) | 2wANOVA | Normal | 99.92 ± 4.67 | 89.98 ± 7.71 | 111.65 ± 4.61 | 3.540 | 0.051 | 0.606 | 0.524 | 0.478 | 0.073 | 3.236 | 0.063 | 0.158 | 0.017 | 0.428 | 0.220 |
| Motor reflexes | |||||||||||||||||
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Test | Data structure | WT | Het | KO | F | p value | Power | F | p value | Power | F | p value | Power | WT vs Het | WT vs KO | Het vsKO | |
| Righting reflex | 2wANOVA | Nonnormal | 0.05 ± 0.05 | 0 ± 0 | 0 ± 0 | 0.721 | 0.491 | 0.165 | 0.727 | 0.398 | 0.133 | 0.721 | 0.491 | 0.165 | − | − | − |
| Hindlimb placing, score | 2wANOVA | Nonnormal | 5.57 ± 0.24 | 5.26 ± 0.34 | 4.21 ± 0.57 | 2.778 | 0.072 | 0.524 | 0.093 | 0.762 | 0.060 | 0.117 | 0.890 | 0.067 | 0.618 | 0.029 | 0.086 |
| Hindlimb placing, latency to climb | 2wANOVA | Nonnormal | 8.29 ± 1.61 | 7.21 ± 1.66 | 10.96 ± 2.57 | 0.836 | 0.439 | 0.186 | 0.333 | 0.567 | 0.087 | 0.117 | 0.890 | 0.067 | − | − | − |
| Hindlimb placing, failed attempts | 2wANOVA | Nonnormal | 0.21 ± 0.12 | 0.36 ± 0.17 | 0.89 ± 0.28 | 2.778 | 0.072 | 0.524 | 0.093 | 0.762 | 0.060 | 0.117 | 0.890 | 0.067 | 0.618 | 0.029 | 0.086 |
| Inverted screen, latency to fall | 2wANOVA | Nonnormal | 33.78 ± 5.09 | 37 ± 4.72 | 9 ± 3.13 | 11.464 | 0.000 | 0.991 | 0.701 | 0.406 | 0.130 | 0.645 | 0.529 | 0.152 | 0.522 | 0.000 | 0.000 |
| Hanging, score | 2wANOVA | Nonnormal | 6.26 ± 0.18 | 6 ± 0.25 | 4.84 ± 0.27 | 10.223 | 0.000 | 0.982 | 2.691 | 0.107 | 0.363 | 0.834 | 0.440 | 0.185 | 0.486 | 0.000 | 0.001 |
| Hanging, latency to fall | 2wANOVA | Nonnormal | 25.44 ± 2.27 | 23.66 ± 2.66 | 8.48 ± 1.05 | 18.838 | 0.000 | 1.000 | 0.269 | 0.606 | 0.080 | 0.816 | 0.448 | 0.182 | 0.643 | 0.000 | 0.000 |
| Grip strength | |||||||||||||||||
| Latency | Test | Data structure | F | p value | Power | WT vs Het | WT vs KO | Het vsKO | |||||||||
| - Session | rMeasures | Sph.viol | 3.520 | 0.033 | 0.644 | − | − | − | |||||||||
| - Session × gen. | rMeasures | Sph.viol | 1.971 | 0.105 | 0.575 | − | − | − | |||||||||
| - Genotype | rMeasures | Sph.viol | 0.324 | 0.725 | 0.099 | − | − | − | |||||||||
| - Cohort | rMeasures | Sph.viol | 47.402 | 0.000 | 1.000 | − | − | − | |||||||||
| - Session × gen. × coh. | rMeasures | Sph.viol | 2.687 | 0.035 | 0.729 | − | − | − | |||||||||
| - Gen. × coh. | rMeasures | Sph.viol | 1.044 | 0.359 | 0.223 | − | − | − | |||||||||
| Genotype | Cohort | Genotype × cohort | Pairwise comparisons | ||||||||||||||
| Individual trials | Test | Data structure | WT | Het | KO | F | p value | Power | F | p value | Power | F | p value | Power | WT vs Het | WT vs KO | Het vsKO |
| Session 1 | 2wANOVA | Normal | 0.94 ± 0.05 | 0.99 ± 0.06 | 1.03 ± 0.06 | 0.502 | 0.608 | 0.128 | 25.973 | 0.000 | 0.999 | 1.564 | 0.219 | 0.317 | − | − | − |
| Session 2 | 2wANOVA | Normal | 0.86 ± 0.07 | 0.85 ± 0.06 | 1.01 ± 0.05 | 2.222 | 0.119 | 0.433 | 36.967 | 0.000 | 1.000 | 1.631 | 0.206 | 0.329 | − | − | − |
| Session 3 | 2wANOVA | Normal | 0.91 ± 0.06 | 0.92 ± 0.06 | 0.89 ± 0.06 | 0.320 | 0.728 | 0.098 | 23.585 | 0.000 | 0.997 | 1.883 | 0.163 | 0.374 | − | − | − |
| Mean strength | 2wANOVA | Normal | 0.9 ± 0.05 | 0.92 ± 0.05 | 0.98 ± 0.04 | 0.324 | 0.725 | 0.099 | 47.402 | 0.000 | 1.000 | 1.044 | 0.359 | 0.223 | − | − | − |
| Highest score | 2wANOVA | Nonnormal | 1.08 ± 0.05 | 1.07 ± 0.05 | 1.13 ± 0.05 | 0.243 | 0.785 | 0.086 | 26.793 | 0.000 | 0.999 | 0.821 | 0.446 | 0.183 | − | − | − |
WT, wild-type mice; Het, heterozygous mice; KO, homozygous knock-out mice. Group values are reported as mean ± SEM. Bold font indicates significant results (p < 0.05). Individual results and statistical analyses for cohorts 1 and 2 are available in Extended Data Table 6-1. 2wANOVA: 2-way ANOVA, rMeasures: repeated measures, Sph.viol: sphericity violated, gen: genotype, coh: cohort.