Figure 3.

Lis1 KO via intraperitoneal tamoxifen injection in adult mice results in a severe phenotype. Lis1 KO mice exposed to tamoxifen invariably displayed spinal kyphosis (A, lower panel) and hind leg clasping (B, right panel). Neither was observed in control animals (CON) at any time. This includes the no Cre, no flLis1, Lis1 KO het, or mock-injected Lis1 KO animals. Both Lis1 KO and control mice were killed as soon as kyphosis and leg clasping became apparent in the KO animals. Phenotypes arose with latencies depending on the specific tamoxifen-dosing regimen (see Materials and Methods). C, Symptom-free survival curves show that the latency is shorter for the 2 × 8 mg regimen (N = 84) compared to the 5 × 2 mg regimen (N = 12). Control mice were killed at the same time as the Lis1 KO mice for recombination and expression studies. However, six no Cre control mice and six no flLis1 control mice receiving the 2 × 8 mg dosing regimen survived symptom free for three weeks before they were killed (total N = 12).