), after an initial delay period suggesting Cu uptake in the CNS is limiting.

SODWT is metal deficient in the brains of SODWTxCCS mice

SOD accumulates as copper deficient in the CNS of mice over-expressing mutant human SOD (Roberts et al., 2014; Williams et al., 2016). To investigate the link between SOD maturity and the early development crisis seen in SODWTxCCS mice, we assayed the maturity of human SODWT in CNS tissue of SODWTxCCS mice. Using native protein mass spectrometry methods previously described by (Rhoads et al., 2011, 2013), we measured the tissue concentrations of six SODWT subspecies differentiated by metal state (apo; 1-metal; Cu,Zn) and C57-C146 disulfide state (SH or S-S). Because immature wild-type human SOD is more stable than comparably immature mutant SOD (Furukawa and O’Halloran, 2005), we reasoned that SODWT would accumulate more readily in immature forms than would SODG93A. In practice though, the final difference between SODWT and SODG93A CNS tissue is not substantial[JM11] , probably because the SODWT gene copy number is much lower than in SODG93A mice.
SODWTxCCS mice at 15 days expressed about 100uM transgenic SODWT in brain. About half the SODWT was Cu, Zn, S-S SODWT, while the other half was mostly 1-metal and disulfide-reduced (SH) (Figure 3). Treating SODWTxCCS mice with CuATSM significantly decreased the fraction of SODWT that was copper-deficient, as well as the fraction that was SH, while not significantly changing the total concentration of SOD.