Distinct Basal Metabolism in Three Mouse Models of Neurodevelopmental Disorders

Cumulative food consumption and activity levels of DS, 16pDel, and FXS mice measured in CLAMS. A–C, Average cumulative food consumption in grams shown over a 24-h cycle for WT and Dp(16)Yey/+ male and female mice (A); WT and 16p11.2^df/+ male and female mice (B); WT and Fmr1 KO (homo/heterozygous) male and female mice (C). D–F, Activity levels (horizontal beam breaks) in CLAMS cages for WT and Dp(16)Yey/+ male and female mice (D); WT and 16p11.2^df/+ male and female mice (E); WT and Fmr1 KO (homo/heterozygous) male and female mice (F). The night phase of testing is depicted by gray shaded area. WT, wild type; DS, Down syndrome; 16pDel, 16p11.2 deletion syndrome; FXS, fragile X syndrome. Data are whisker boxes (min to max, center line indicating median) in A–C, or mean ± SEM in D–F (n = 10 animals per group); *p < 0.05 (two-way ANOVA and Sidak’s post hoc test). ♂: males; ♀: females.

VO₂ by DS, 16pDel, and FXS mice measured in CLAMS. A–C, Absolute values of average VO₂ during day (light) and night (dark) in WT and Dp(16)Yey/+ male and female mice (A); WT and 16p11.2^df/+ male and female mice (B); WT and Fmr1 KO (homo/heterozygous) male and female mice (C). D–F, Average VO₂ during day and night normalized to body weight in WT and Dp(16)Yey/+ male and female mice (D); WT and 16p11.2^df/+ male and female mice (E); WT and Fmr1 KO (homo/heterozygous) male and female mice (F). G–I, Average VO₂ during day and night normalized to lean mass in WT and Dp(16)Yey/+ male and female mice (G); WT and 16p11.2^df/+ male and female mice (H); WT and Fmr1 KO (homo/heterozygous) male and female mice (I). The night phase of testing is depicted by gray shaded areas. WT, wild type; DS, Down syndrome; 16pDel, 16p11.2 deletion syndrome; FXS, fragile X syndrome. Data are whisker boxes (min to max, center line indicating median); n = 10 animals per group. Asterisks depict significant differences between groups; *p < 0.05, **p < 0.01, ***p < 0.001 (two-way ANOVA and Sidak’s post hoc test); p value is indicated when approaching significance. ♂: males; ♀: females.

VCO₂ by DS, 16pDel, and FXS mice measured in CLAMS. A–C, Absolute values of average VCO₂ during day (light) and night (dark) in WT and Dp(16)Yey/+ male and female mice (A); WT and 16p11.2^df/+ male and female mice (B); WT and Fmr1 KO (homo/heterozygous) male and female mice (C). D–F, Average VCO₂ during day and night normalized to body weight in WT and Dp(16)Yey/+ male and female mice (D); WT and 16p11.2^df/+ male and female mice (E); WT and Fmr1 KO (homo/heterozygous) male and female mice (F). G–I, Average VCO₂ during day and night normalized to lean mass in WT and Dp(16)Yey/+ male and female mice (G); WT and 16p11.2^df/+ male and female mice (H); WT and Fmr1 KO (homo/heterozygous) male and female mice (I). The night phase of testing is depicted by gray shaded areas. WT, wild type; DS, Down syndrome; 16pDel, 16p11.2 deletion syndrome; FXS, fragile X syndrome. Data are whisker boxes (min to max, center line indicating median); n = 10 animals per group. Asterisks depict significant differences between groups; *p < 0.05, **p < 0.01, ***p < 0.001 (two-way ANOVA and Sidak’s post hoc test); p value is indicated when approaching significance. ♂: males; ♀: females.

RER from DS, 16pDel, and FXS mice. A–C, RER calculated from absolute values during day (light) and night (dark) in WT and Dp(16)Yey/+ male and female mice (A); WT and 16p11.2^df/+ male and female mice (B); WT and Fmr1 KO (homo/heterozygous) male and female mice (C). The night phase of testing is depicted by gray shaded areas. The dotted line depicts a RER of 1. WT, wild type; DS, Down syndrome; 16pDel, 16p11.2 deletion syndrome; FXS, fragile X syndrome. Data are whisker boxes (min to max, center line indicating median); n = 10 animals per group. Asterisks depict significant differences between groups; *p < 0.05, **p < 0.01 (two-way ANOVA and Sidak’s post hoc test); p value is indicated when approaching significance. ♂: males; ♀: females.

CE by DS, 16pDel, and FXS mice measured in CLAMS. A–C, Absolute values of average CE during day (light) and night (dark) in WT and Dp(16)Yey/+ male and female mice (A); WT and 16p11.2^df/+ male and female mice (B); and WT and Fmr1 KO (homo/heterozygous) male and female mice (C). D–F, Average CE during day and night normalized to body weight in WT and Dp(16)Yey/+ male and female mice (D); WT and 16p11.2^df/+ male and female mice (E); and WT and Fmr1 KO (homo/heterozygous) male and female mice (F). G–I, Average CE during day and night normalized to lean mass in WT and Dp(16)Yey/+ male and female mice (G); WT and 16p11.2^df/+ male and female mice (H); and WT and Fmr1 KO (homo/heterozygous) male and female mice (I). The night phase of testing is depicted by gray shaded areas. WT, wild type; DS, Down syndrome; 16pDel, 16p11.2 deletion syndrome; FXS, fragile X syndrome. Data are whisker boxes (min to max, center line indicating median); n = 10 animals per group. Asterisks depict significant differences between groups; *p < 0.05, **p < 0.01, ***p < 0.001 (two-way ANOVA and Sidak’s post hoc test). ♂: males; ♀: females.

Plasma metabolite levels in DS mice measured by LC-MS. WT, wild type. Data are mean ± SEM; n = 5–6 animals per group. Asterisks depict significant differences between groups; *p < 0.05, **p < 0.01, ***p < 0.001 (two-way ANOVA and Tukey’s post hoc test).

Plasma metabolite levels in 16pDel mice measured by LC-MS. WT, wild type. Data are mean ± SEM; n = 5 animals per group. Asterisks depict significant differences between groups; *p < 0.05, **p < 0.01, ***p < 0.001 (two-way ANOVA and Tukey’s post hoc test).