[JM5] 
Figure 1 - SODWTxCCS mice die early, are rescued by CuATSM. Caption pending figure replacement.

COX is deficient, likely cause for early death

It has been proposed that the early death seen in SODG93AxCCS mice is a result of cytochrome c oxidase (COX) deficiency caused by redistribution of copper, via CCS, to SOD instead of COX (Williams et al., 2016). We assayed COX activity in CNS tissue from SODWTxCCS mice to investigate the link with the early development crisis.
SODWTxCCS mice exhibited diminished COX activity compared to CCS littermates, which were in turn similar to nontransgenic animals (Figure 2). Treating SODWTxCCS mice with CuATSM restored some COX activity, but levels remained below those of CCS or nontransgenic mice. SODWT-overexpressing mice also exhibited diminished COX activity compared to CCS or nontransgenic mice, though less severe[JM6] . Contrary to previous reports, these results suggest that overexpression of SODWT, especially with CCS, is capable of disturbing copper homeostasis, which manifests as COX deficiency.