The expression of a truncated HMGI-C gene induces gigantism associated with lipomatosis

Rearrangements of the HMGI-C gene have frequently been detected in human be nign tumors of mesenchymal origin, including lipomas. The HMGI-C protein ha s three AT-hook domains and an acidic COOH-terminal tail, The HMGI-C modifi cations consist in the loss of the C-tail and the fusion with ectopic seque nces, Recent results show that the loss of the COOH-terminal region, rather than the acquisition of new sequences, is sufficient to confer to HMGI-C t he ability to transform NIH3T3 cells. Therefore, transgenic mice carrying a HMGI-C construct (HMGI-C/T), containing only the three AT-hook domains, we re generated. The HIMGI-C/T mice showed a giant phenotype, together,vith a predominantly abdominal/pelvic lipomatosis, suggesting a pivotal role of th e HMGI-C truncation in the generation of human lipomas.