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( A ) Schematic illustration of the behavioral tests performed on young adult (P42–P56) heterozygous Trio variant mice of both sexes. All mice proceeded through the same battery of tests. ( B ) +/K1431M and +/K1918X mice of both sexes had decreased latency to fall off an accelerating <t>rotarod</t> compared to WT male mice. In male mice (left), linear regressions identified differences from WT in slopes, indicating impaired rate of improvement in the skill (WT 16.96±1.344; +/K1431M 7.270±2.019, p<0.0001; +/K1918X 10.61 ± 1.444, p<0.0001; #### p<0.0001) (n=40 WT; 10 +/K1431M ; 16 +/K1918X ; 13 +/M2145T male mice). In female mice (right), linear regressions identified differences from WT in slopes ( +/K1431M 9.436±2.146, p=0.0215; vs WT 14.52±1.792; # p<0.05) and intercepts ( +/K1918X 6.492 ± 5.555, p=0.0248; vs WT 19.28±5.942; € p<0.05; n=28 WT; 11 +/K1431M ; 16 13 +/K1918X ; and 15 +/M2145T female mice). ( C ) +/K1431M mice of both sexes and +/K1918X females showed impaired social interactions in a three-chamber test, showing no preference to the (Str.) vs. inanimate object (Obj.) compared to WT. ( D ) +/K1918X mice of both sexes and +/M2145T females exhibit impaired novel object recognition and spend equal time exploring a novel object ( N ) and a familiar object ( F ). ( E ) Male +/K1918X mice exhibited increased nestlet shredding over 30 min (26.26 ± 3.61% shredded vs WT 14.26 ± 2.97%; p=0.0433), and +/K1431M mice exhibited a trend toward increased nestlet shredding (25.90 ± 4.34% shredded, p=0.1038) compared to WT mice. n=19 male, 19 female WT; 10 male, 10 female +/K1431M ; 15 male, 11 female +/K1918X ; 9 male, 10 female +/M2145T mice. All data are shown as mean ± SEM, significant differences identified using two-way ANOVA with post-hoc Bonferroni MC ( ns p <0.1, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001). Numbers of mice quantified per group are annotated inside the bar unless otherwise indicated.
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( A ) Schematic illustration of the behavioral tests performed on young adult (P42–P56) heterozygous Trio variant mice of both sexes. All mice proceeded through the same battery of tests. ( B ) +/K1431M and +/K1918X mice of both sexes had decreased latency to fall off an accelerating <t>rotarod</t> compared to WT male mice. In male mice (left), linear regressions identified differences from WT in slopes, indicating impaired rate of improvement in the skill (WT 16.96±1.344; +/K1431M 7.270±2.019, p<0.0001; +/K1918X 10.61 ± 1.444, p<0.0001; #### p<0.0001) (n=40 WT; 10 +/K1431M ; 16 +/K1918X ; 13 +/M2145T male mice). In female mice (right), linear regressions identified differences from WT in slopes ( +/K1431M 9.436±2.146, p=0.0215; vs WT 14.52±1.792; # p<0.05) and intercepts ( +/K1918X 6.492 ± 5.555, p=0.0248; vs WT 19.28±5.942; € p<0.05; n=28 WT; 11 +/K1431M ; 16 13 +/K1918X ; and 15 +/M2145T female mice). ( C ) +/K1431M mice of both sexes and +/K1918X females showed impaired social interactions in a three-chamber test, showing no preference to the (Str.) vs. inanimate object (Obj.) compared to WT. ( D ) +/K1918X mice of both sexes and +/M2145T females exhibit impaired novel object recognition and spend equal time exploring a novel object ( N ) and a familiar object ( F ). ( E ) Male +/K1918X mice exhibited increased nestlet shredding over 30 min (26.26 ± 3.61% shredded vs WT 14.26 ± 2.97%; p=0.0433), and +/K1431M mice exhibited a trend toward increased nestlet shredding (25.90 ± 4.34% shredded, p=0.1038) compared to WT mice. n=19 male, 19 female WT; 10 male, 10 female +/K1431M ; 15 male, 11 female +/K1918X ; 9 male, 10 female +/M2145T mice. All data are shown as mean ± SEM, significant differences identified using two-way ANOVA with post-hoc Bonferroni MC ( ns p <0.1, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001). Numbers of mice quantified per group are annotated inside the bar unless otherwise indicated.
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Image Search Results


( A ) Schematic illustration of the behavioral tests performed on young adult (P42–P56) heterozygous Trio variant mice of both sexes. All mice proceeded through the same battery of tests. ( B ) +/K1431M and +/K1918X mice of both sexes had decreased latency to fall off an accelerating rotarod compared to WT male mice. In male mice (left), linear regressions identified differences from WT in slopes, indicating impaired rate of improvement in the skill (WT 16.96±1.344; +/K1431M 7.270±2.019, p<0.0001; +/K1918X 10.61 ± 1.444, p<0.0001; #### p<0.0001) (n=40 WT; 10 +/K1431M ; 16 +/K1918X ; 13 +/M2145T male mice). In female mice (right), linear regressions identified differences from WT in slopes ( +/K1431M 9.436±2.146, p=0.0215; vs WT 14.52±1.792; # p<0.05) and intercepts ( +/K1918X 6.492 ± 5.555, p=0.0248; vs WT 19.28±5.942; € p<0.05; n=28 WT; 11 +/K1431M ; 16 13 +/K1918X ; and 15 +/M2145T female mice). ( C ) +/K1431M mice of both sexes and +/K1918X females showed impaired social interactions in a three-chamber test, showing no preference to the (Str.) vs. inanimate object (Obj.) compared to WT. ( D ) +/K1918X mice of both sexes and +/M2145T females exhibit impaired novel object recognition and spend equal time exploring a novel object ( N ) and a familiar object ( F ). ( E ) Male +/K1918X mice exhibited increased nestlet shredding over 30 min (26.26 ± 3.61% shredded vs WT 14.26 ± 2.97%; p=0.0433), and +/K1431M mice exhibited a trend toward increased nestlet shredding (25.90 ± 4.34% shredded, p=0.1038) compared to WT mice. n=19 male, 19 female WT; 10 male, 10 female +/K1431M ; 15 male, 11 female +/K1918X ; 9 male, 10 female +/M2145T mice. All data are shown as mean ± SEM, significant differences identified using two-way ANOVA with post-hoc Bonferroni MC ( ns p <0.1, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001). Numbers of mice quantified per group are annotated inside the bar unless otherwise indicated.

Journal: eLife

Article Title: Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice

doi: 10.7554/eLife.103620

Figure Lengend Snippet: ( A ) Schematic illustration of the behavioral tests performed on young adult (P42–P56) heterozygous Trio variant mice of both sexes. All mice proceeded through the same battery of tests. ( B ) +/K1431M and +/K1918X mice of both sexes had decreased latency to fall off an accelerating rotarod compared to WT male mice. In male mice (left), linear regressions identified differences from WT in slopes, indicating impaired rate of improvement in the skill (WT 16.96±1.344; +/K1431M 7.270±2.019, p<0.0001; +/K1918X 10.61 ± 1.444, p<0.0001; #### p<0.0001) (n=40 WT; 10 +/K1431M ; 16 +/K1918X ; 13 +/M2145T male mice). In female mice (right), linear regressions identified differences from WT in slopes ( +/K1431M 9.436±2.146, p=0.0215; vs WT 14.52±1.792; # p<0.05) and intercepts ( +/K1918X 6.492 ± 5.555, p=0.0248; vs WT 19.28±5.942; € p<0.05; n=28 WT; 11 +/K1431M ; 16 13 +/K1918X ; and 15 +/M2145T female mice). ( C ) +/K1431M mice of both sexes and +/K1918X females showed impaired social interactions in a three-chamber test, showing no preference to the (Str.) vs. inanimate object (Obj.) compared to WT. ( D ) +/K1918X mice of both sexes and +/M2145T females exhibit impaired novel object recognition and spend equal time exploring a novel object ( N ) and a familiar object ( F ). ( E ) Male +/K1918X mice exhibited increased nestlet shredding over 30 min (26.26 ± 3.61% shredded vs WT 14.26 ± 2.97%; p=0.0433), and +/K1431M mice exhibited a trend toward increased nestlet shredding (25.90 ± 4.34% shredded, p=0.1038) compared to WT mice. n=19 male, 19 female WT; 10 male, 10 female +/K1431M ; 15 male, 11 female +/K1918X ; 9 male, 10 female +/M2145T mice. All data are shown as mean ± SEM, significant differences identified using two-way ANOVA with post-hoc Bonferroni MC ( ns p <0.1, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001). Numbers of mice quantified per group are annotated inside the bar unless otherwise indicated.

Article Snippet: A five-lane rotarod treadmill (Med Associates ENV-577M 8.75’’ rod circumference) was used for accelerating analyses.

Techniques: Variant Assay, Battery