Conditional loss of PTEN leads to skeletal abnormalities and lipoma formation.

To understand the role of tumor suppressor PTEN in cartilage development, we have generated chondrocyte specific PTEN deletion mice using Col2a1Cre and PTEN(loxp/loxp) mice. PTEN mutant mice are viable and fertile, nonetheless, develop kyphosis over time. Histological analyses show mutant vertebrae and intervertebral discs are larger and therefore the spines are longer than in control mice. In addition, the growth plates are thicker, invading trabecular bone areas are deeper, and marrow adipocyte populations are higher in PTEN mutant mice. Furthermore, the growth plates, not normally fused in mouse long bones, are fused in PTEN mutants. Intriguingly, PTEN mice develop lipomas and show abnormal accumulation of fat tissues along spines. Cell tracking assays have confirmed that lipomas and a portion of fat tissues were derived from Col2a1Cre PTEN(loxp/loxp) cells. Further analyses have suggested that the phenotypes of PTEN mutant likely attribute to PTEN's negatively regulating role in PI3K/Akt pathway.