Antecedent presentation of neurological phenotypes in the Collaborative Cross reveals four classes with complex sex-dependencies

Figures

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  Figure 1. Weight changes during first week post-infection. Average post-infection weight changes during the first 7 dpi demonstrated varied levels of susceptibility to TMEV-induced weight loss.

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  Figure 2. Onset of delayed righting reflex. Strains differed by date of first observation of delayed righting reflex, indicating a delayed motor response.

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  Figure 3. Progression of neurological phenotypes varied by strain. Observation frequencies for qualitative phenotypes (righting reflex, paresis, paralysis, dystonia, and sickness/pain) were compiled together for 14 dpi and 90 dpi and the differences from 14–90 dpi compared to visualize how each strain fared throughout the chronic phase of TMEV infection (“progression score”). Strains included in each successive progression score are delineated by brackets.

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  Figure 4. Gait parameters were affected differently depending on mouse strain. Pearson correlation clustering revealed two major clusters, 1 (green bar) and 2 (orange bar), which distinguish between strains with significantly different gait parameter measurements. Each individual parameter was categorized based on the primary gait characteristic it measured58–60; categories for each parameter are listed in Table S5. The two clusters do not include those strains for which sex was a major influence on gait parameters. The results shown here include data from infected mice at all time points; additional granularity (e.g. separate time points and sexes) is described in the text and shown in figures included in Figs. S4 and S5.

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  Figure 5. Principal component analysis showed that both infection and sex influenced phenotypes. Principal component analysis (PCA) based on 538 qualitative measurements (phenotypic traits) in mice from 18 strains revealed greater dispersion of qualitative phenotypes in infected vs. uninfected mice. Greater phenotypic dispersion was also seen in males compared to females in each treatment group.