Transgenic Mice Expressing a Truncated Form of the High Mobility Group I-C Protein Develop Adiposity and an Abnormally High Prevalence of Lipomas

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 r...

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Bibliographic Details
Published in:The Journal of biological chemistry 2000-05, Vol.275 (19), p.14394-14400
Main Authors: Arlotta, Paola, Tai, Albert K.-F., Manfioletti, Guidalberto, Clifford, Charles, Jay, Gilbert, Ono, Santa Jeremy
Format: Article
Language:English
Subjects:
Adipocytes - metabolism
Adipose Tissue
Animals
Base Sequence
Cytoskeletal Proteins - genetics
DNA - metabolism
DNA Primers
Gene Expression
high mobility group protein I(C)
High Mobility Group Proteins - genetics
High Mobility Group Proteins - metabolism
Humans
lipoma
Lipoma - genetics
Mice
Mice, Transgenic
Protein Binding
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M000564200