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. Author manuscript; available in PMC: 2024 May 3.
Published in final edited form as: Neuron. 2023 Mar 1;111(9):1423–1439.e4. doi: 10.1016/j.neuron.2023.02.004

Figure 3. Editing of WT Hspa8 to the G470R variant is sufficient to protect against severe SMA.

Figure 3.

(A) Sequence chromatograms highlighting the ancestral (GGG) and edited (CGG) codons in Hspa8 from severe and modified SMA mutants. Hspa8G470R-expressing mutants are (B) larger, (C) perform significantly better in a motor performance assay and (D) have markedly longer lifespans than do mutants expressing the WT protein. Note: *, **, ***, P < 0.05, P < 0.01, P < 0.001 respectively; t tests (SMA and SMA-G470R+/+), one-way ANOVA and log-rank test respectively for panels B, C and D. (E) Representative immunostains of lumbar spinal cord sections depicting normal numbers of motor neurons in the SMA-G470R mutant at PND9. (F) Morphometric counts of lumbar motor neurons in SMA and littermate controls. (G) H&E-stained muscle sections from PND9 SMA mutants with or without the G470R variant and a littermate control; myofibers in the SMA-G470R+/+ mouse are larger than those of the SMA mutant. (H) Frequency distributions and (I) average sizes of myofiber in PND9 SMA and littermate controls. (J) Graph of mean myofiber areas in young adult (PND75) SMA-G470R+/+ mutants and littermate controls. Note: *, **, ***, P < 0.05, P < 0.01, P < 0.001 respectively; one-way ANOVA for comparisons at PND9 and t tests for comparisons at PND75 in panels F, I and J. N.S. – not significant. Scale bars: 20μm (panel E), 25μm (panel G). Data: mean ± SEM. See also Fig. S4.