Fig. 6.

The CHOP null mutation provides early protection from loss of phenotype, but not from neuron death, in the chronic MPTP model. (a) Wild-type and CHOP null adult mice were injected with saline or MPTP (30 mg/kg/day) for 5 days (n = 4 each group except wild-type saline, n = 3) and killed 4 days after the last dose for immunostaining and stereologic determination of TH-positive neuron number. Remarkably, there was minimal apparent effect in the CHOP nulls treated with MPTP. The wild-type mice showed a 65% decrease in number of TH-positive profiles. This difference could not be attributed to a change in the magnitude of apoptosis, as discussed in the text. (b) Representative low power photomicrographs demonstrating the resistance of SN dopamine neurons in CHOP null mice to the early effect (4 days post-lesion) of MPTP in the chronic injection model. These sections are derived from mice studied by stereologic analysis of TH-positive neuron number, shown in (a). Bar 300 μm. (c) Wild-type and CHOP null mice were injected with saline=or MPTP (n = 4–5 each group) and killed 21 days following the final injection for TH immunostaining and stereology. At this late post-lesion day, when the acute suppression of phenotype has recovered, it is apparent that there has been only a 36% loss of SN dopamine neurons in wild-type mice. While there was a trend for a reduction in the number of neurons lost in the CHOP null mice (29% loss), this did not achieve significance (p > 0.5, Tukey post-hoc).