Figure 7.
GPT2 is the critical mediator of pro-anabolic action of thyroid hormone in denervation-induced atrophy
(A) Diagrammatic representation of breeding for the generation of GPT2 KO mice and pictures of TA, soleus, and GC of GPT2 KO+/– and WT mice together with a graphical representation of the loss (Δ) muscle weight expressed as the percentage compared with WT.
(B) H&E, laminin immunofluorescence, and Sirius red staining of GPT2 KO+/– and WT TA muscles. Scale bar, 50 μm.The CSA (1) and quantification of the Sirius red density (2) relative to WT muscles is reported below.
(C) Pictures of TA, soleus, and GC muscles after 6 days of denervation from GPT2 KO+/– and WT mice. (Bottom) The graphical representation of Δ muscle weight expressed as the percentage compared with the innervated contralateral muscle in the same mouse. n ≥ 8 mice for GPT2 KO+/– and WT CTR littermates.
(D) Timeline of TH treatment and denervation experiments in GPT2 KO+/– and WT mice. H&E and laminin staining of euthyroid denervated (DEN) and hyperthyroid denervated (DEN + TH) WT and GPT2 KO+/– mice with respect to CTR euthyroid innervated TA muscles. Scale bar, 50 μm.
(E) CSA of the same muscles as in (D)
(F–J) mRNA expression levels of the indicated genes and MHC class II/MHC class I mRNA ratio in GC muscles as in (D). Levels of indicated genes are relative to Cyclophilin-A mRNA used as an internal CTR and normalized to the CTR euthyroid muscle. Data represent the mean ± SD of the mean of nine replicates. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.
