Transgenic mice expressing a truncated form of the high mobility group I-Cprotein develop adiposity and an abnormally high prevalence of lipomas

Chromosomal translocations in human lipomas frequently create fusion transc ripts encoding high mobility group (HMG) I-C DNA-binding domains and C-term inal sequences from different presumed transcription factors, suggesting a potential role for HMG I-C in the development of lipomas. To evaluate the r ole of the HMG I-C component, the three DNA-binding domains of HMG I-C have now been expressed in transgenic mice. Despite the ubiquitous expression o f the truncated HMG I-C protein, the transgenic mice develop a selective ab undance of fat tissue early in life, show marked adipose tissue inflammatio n, and have an abnormally high incidence of lipomas. These findings demonst rate that the DNA-binding domains of HMG I-C, in the absence of a C-termina l fusion partner, are sufficient to perturb adipogenesis and predispose to lipomas. We provide data supporting the central utility of this animal mode l as a tool to understand the molecular mechanisms underlying the developme nt of one of the most common kind of human benign tumors.