Osteogenic tumours in Lkb1-deficient mice

Abstract

Germline mutation in LKB1 is the cause of Peutz–Jeghers Syndrome in humans, a rare disorder predisposing to cancer and multiple gastrointestinal hamartomous polyps. Mice harboring a germline inactivating Lkb1 mutation develop similar gastrointestinal polyps and liver neoplasia. We observed paralysis in ∼ 2% of Lkb1 +/− mice on two genetic backgrounds, C57BL/6J and 129/sv, at around 300 days of age. Stepped serial sectioning of the whole spinal column found multiple osteogenic tumours that were lobulated, showed osteoid formation and had an infiltrative growth pattern, which extended into the surrounding muscle. Osteogenic tumours were also present in asymptomatic Lkb1 +/− mice ( n = 12) in the lateral spinous processes, spinous vertebral bodies and the bodies of sacral tail vertebrae. Although asymptomatic, the proliferation in several mice caused a narrowing and compression of the spinal canal. The long bones of Lkb1 +/− mice had osteoblastosis within the femur and tibia indicating that the process is multi-focal; bone remodelling was accompanied by angiogenesis. No wild type Lkb1 +/+ siblings ( n = 12) showed aberrant osteoblastosis or bone remodelling. This is the first report of multifocal osteoblastic tumours in Lkb1 +/− mice and our observations indicate that Lkb1, like Pten, may have a distinct role in controlling osteoblast proliferation in the mouse.