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

Abstract

Chromosomal translocations in human lipomas frequently create fusion transcripts encoding high mobility group (HMG) I-C DNA-binding domains and C-terminal sequences from different presumed transcription factors, suggesting a potential role for HMG I-C in the development of lipomas. To evaluate the role 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 of the truncated HMG I-C protein, the transgenic mice develop a selective abundance of fat tissue early in life, show marked adipose tissue inflammation, and have an abnormally high incidence of lipomas. These findings demonstrate that the DNA-binding domains of HMG I-C, in the absence of a C-terminal fusion partner, are sufficient to perturb adipogenesis and predispose to lipomas. We provide data supporting the central utility of this animal model as a tool to understand the molecular mechanisms underlying the development of one of the most common kind of human benign tumors.

• Authors: P Arlotta, A K Tai, G Manfioletti, C Clifford, G Jay, S J Ono
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 275 Issue 19 Pg. 14394-400 (May 12 2000) ISSN: 0021-9258 [Print] United States
• PMID: 10747931 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cytoskeletal Proteins
• DNA Primers
• High Mobility Group Proteins
• DNA

Topics

• Adipocytes (metabolism)
• Adipose Tissue
• Animals
• Base Sequence
• Cytoskeletal Proteins (genetics)
• DNA (metabolism)
• DNA Primers
• Gene Expression
• High Mobility Group Proteins (genetics, metabolism)
• Humans
• Lipoma (genetics)
• Mice
• Mice, Transgenic
• Protein Binding