Figure 6.
Assessment of phenotypic progression in DTA mice. (A) SSEP waveforms. Each SSEP trace represents the average of 25–30 evoked responses recorded from the L4–L5 intervertebral space (low lumbar level) or T5–T6 intervertebral space (mid-thoracic level) following stimulation of the tibial nerve at the ankle. (B) Statistical analysis of the SSEP parameters: peak latency (Lat) and Δlatency (ΔLat, difference between the T5–T6 and L4–L5 peak latencies) and amplitude (Amp). In DTA mice at 35 dpi, peak latencies are prolonged and Δlatencies are increased, while amplitudes are decreased, indicating severe conduction defects, both in the PNS and CNS of these mice. At 70–77 dpi, the amplitudes observed in DTA mice reach values comparable to controls, but though improved in comparison to 35 dpi values, a milder defect in peak latency time lingers. At 35 dpi, three of the eight DTA mice did not demonstrate recordable T5–T6 responses, indicating a central conduction failure. The statistical analysis of T5–T6 recordings does not include those with absent responses. Graphs indicate mean ± SEM. For 35 dpi, n = 7–8, *P < 0.005, **P < 0.0001. For 70–77 dpi, n = 6–7, *P < 0.03; **P < 0.008. (C) The DTA mice were unable to perform on the rotarod at 35 and 42 dpi. They began showing a gradual improvement at 49 dpi that continued until 77 dpi, when their latencies became similar to control mice. Graphs indicate mean ± SD, n = 5 mice for DTA and n = 4 for controls, *P < 0.08, **P < 0.007 (two-tailed t-test).