Figure 6. Alterations in the expression of the FoxO family of transcription factors and its targets in cardiac muscle of symptomatic stage SMA model mice are restricted to the severe Smn^−/−; SMN2 strain.

(a,c) Increased Atrogin-1 (p = 0.018), but not MuRF1, mRNA levels are observed in Smn^−/−; SMN2 hearts at P5. However, this is not accompanied by an increase in the level of ubiquitinated proteins. (b,d) The levels of Atrogin-1 and MuRF1 mRNA are not altered in hearts from P21 Smn^2B/− mice. Similarly, there was no change in the level of ubiquitinated proteins. (e,f) Gabarapl1, CathepsinL and Bnip3 mRNA levels are elevated in P5 Smn^−/−; SMN2 hearts (p = 0.0076, 0.033, and 0.0075, respectively) but not in P21 Smn^2B/− hearts, although there was a trend towards an increase in all autophagosomal markers. (g,h) No change in LC3-II or P62 protein levels in the hearts of either model. (i,j) An increase in the mRNA level of some of the FoxO transcriptional factor family is observed in hearts from P5 Smn^−/−; SMN2 mice (FoxO3, p = 0.0069 and FoxO4, p = 0.025) but not in hearts from P21 Smn^2B/− mice. (N = 4 for all experiments; p ≤ 0.05 for * and p ≤ 0.01 for **).