Mice expressing MCL1 as a transgene develop massive lymph node enlargement on long-term observation.

(A) Kaplan-Meier probability of remaining free of massive lymph node enlargement. The probability of developing lymph node disease was greater in transgenic (Trans) as compared with nontransgenic (Nontrans) animals (P ≤ .001). Transgenic animals developed either localized or disseminated disease, whereas nontransgenic animals demonstrated localized disease only [a single mass in the mesenteric area (3 animals), 2 mesenteric masses (2 animals), or extranodal lymphoma in the gastrointestinal tract (3 animals)]. The last time point represents animals assayed at 25 to 27 months. (B-C) Expression of the transgene-encoded human MCL1 protein in diseased lymph nodes. Diseased lymph nodes and control tissues were subjected to Western blotting using an antibody directed against human MCL1. The upper photograph shows samples from 3 separate diseased lymph nodes and the spleen from the same transgenic mouse (lanes 1-4), along with lymphoid tissue from a nontransgenic littermate (lane 5). The lower photograph shows diseased lymph nodes from additional transgenic animals with disseminated disease, along with spleen from transgenic animals not exhibiting disseminated disease (lanes 6-7) and ML-1 cells treated with TPA (lane 8). Diseased lymph nodes from transgenic animals with localized disease exhibited levels of MCL1 expression in the same range as the cases with disseminated disease, whereas anMCL1 band was not detected with this antibody in the rare tumors that occurred in nontransgenic animals. Each lane represents 2 × 10⁶ cells in the upper photograph and 5 × 10⁵ cells in the lower photograph.