Results

SODWTxCCS mice die in <21 days, are rescued by CuATSM

We previously showed that mice co-expressing CCS with a large number of copies[JM1]  of SODG93A experienced an early development crisis that is rescuable by treatment with CuATSM. Here we report that mice co-expressing CCS with SODWT [JM2] also experience an early development crisis that is rescuable by treatment with CuATSM. SODWTxCCS pups were identifiable as runts compared to CCS littermates within 6 days after birth. Locomotive deficits such as dragging rear legs and falling over began to manifest immediately around the time littermates started to walk, or about 10 days after birth. By 15 days, most SODWTxCCS pups were immobile and unable to right themselves. SODWTxCCS mice died at an average of ??? days without intervention (Figure 1). SODWTxCCS mice have previously been reported to be symptom-free (Son et al., 2007), yet here we report that they exhibit symptoms similar to those of SODG93AxCCS animals (described by Son et al., 2007; Williams et al., 2016). Our CCS-expressing mice (without human SOD) are indistinguishable from nontransgenic animals, as previously reported.
Continuous treatment with CuATSM rescued the early development crisis seen in SODWTxCCS mice and extended survival beyond 400 [JM3] days (Figure 1). Interestingly, treatment from 6 days until weaning at 21 days was also sufficient to rescue the early development crisis in SODWTxCCS mice, and animals in this group continued to live to ??? [JM4] days without further treatment.