Figure 6.

Increasing toxicity with decreasing huntingtin length. In the presence of tamoxifen, progressive truncation of huntingtin resulted in increased cellular toxicity (P < 0.01). Interestingly, this trend was seen for proteins containing both 15 and 128 polyglutamines (P < 0.01). 293T cells were transfected with each huntingtin construct, or LacZ control, and cell viability in response to apoptotic stress was measured using a modified MTT assay and presented relative to control (untransfected). All wells were transfected with 0.1 μg DNA except for those transfected with the 436-15 and 128 constructs, where 0.08 μg of DNA was used because all the cells died with 0.1 μg DNA. Results for the 436 construct are normalized, taking into account decreased DNA concentration. Asterisks indicate the level of significance between huntingtin containing 15 and 128 glutamines: * P < 0.01; ** P < 0.001.