Figure 10.

Relationship of tau species to motor deficits in JNPL3 mice. A, Multimers were detected in spinal cord extracts from 2-month-old JNPL3 mice (1–3) but were absent in nontransgenic littermates (NT). Asterisk marks nonspecific band also present in nontransgenic littermates, which is attributable to nonspecific binding of the secondary antibody. B, Spinal cord and brain extracts from JNPL3 female mice at the age of 12 (1) and 14 months (2). Tau multimers (tau170 and tau140) and 64 kDa tau species are present in spinal cord but are not clearly visible in brain. C, Tau multimers (tau170 and tau140) and hyperphosphorylated 64 kDa are detected in JNPL3 mice severely affected with motor dysfunction, but neither of these species is seen in unaffected JNPL3 mice of similar age. D, Tau multimers are not present in mice overexpressing wild-type human tau. wt tau, Spinal cord extracts from mice overexpressing wild-type human tau (JN25 line) at 14-months of age; JNPL3, spinal cord extracts from 14-month-old JNPL3 mice. Note that there is no evidence of tau multimers in mice expressing human wild-type tau, despite significantly higher levels of total tau being loaded onto the blot, compared with JNPL3 mice. The apparent low level of tau 55/64 kDa in the JNPL3 mice seen on this Western blot is only attributable to this adjustment (∼3 times more protein was loaded for wild-type tau).