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.