Figure 2. Motor impairment, hyperphagia and spinal motor neuronal transcriptomic changes in mutant mice.
(a) Rotarod and (b) weights of Cohort 1 mice (n = 14 wild-type, 13 TDP-43Q331K/+ and 13 TDP-43Q331K/Q331K mice). (a) Pairwise comparisons: wild-type vs. TDP-43Q331K/+: P=0.014 (*); wild-type vs. TDP-43Q331K/Q331K: P=0.0024 (**). (b) Pairwise comparisons: wild-type vs. TDP-43Q331K/+: P=0.002 (**); wild-type vs. TDP-43Q331K/Q331K: P=0.0002 (***).
(c) Weekly food consumption over 9 weeks (n = 2 cages per genotype). Comparison: Genotype: P=0.047(*).
(d) Rotarod of weight-matched Cohort 2 mice (n = 16 wild-type, 13 TDP-43Q331K/+ and 15 TDP-43Q331K/Q331K mice).
For (a-d) repeated measures two-way ANOVA followed by Holm-Sidak post-hoc test for pairwise comparisons.
(e) Nissl-stained lumbar motor neurons of 5-month-old mice. Representative images shown. Scale bar, 40μm.
(f) Quantification of lumbar motor neurons (n = 4 mice per genotype). Comparison: P=0.089 (ns); unpaired t test.
(g) Examples of isometric twitch force recordings during graded nerve stimulation of FDB muscles from representative wild-type and TDP-43Q331K/Q331K mice. Each increment corresponds to recruitment of motor units of successively higher electrical threshold (n = 5 mice per genotype).
(h) MA plot and (i) hierarchical clustering of significantly differentially expressed genes (DEGs) in laser-captured motor neurons. In (h) blue dots indicate significant changes, red dots indicate intensity hits. In (i) Genes Aox1 and Agrin are labelled. Comparison: DESeq2 wild-type v TDP-43Q331K/Q331K
(j) Immunohistochemistry for AOX1. Representative images from a 5-month-old wild-type mouse shown. Scale bars, 10μm motor neuron, 100μm ventral root.
(k) AOX1 immunofluorescence in lumbar motor neurons. Comparison: P=0.433 (ns); unpaired t test.
For (h-k) n = 4 mice per genotype.
All error bars denote mean ± s.e.m.