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 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.
Arlotta
P
P
Schepens Eye Research Institute, Division of Rheumatology, Immunology & Allergy, Department of Medicine, Brigham & Women's Hospital, and Committee on Immunology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Tai
A K
AK
Manfioletti
G
G
Clifford
C
C
Jay
G
G
Ono
S J
SJ
D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue; D000818:Animals; D001483:Base Sequence; D003598:Cytoskeletal Proteins / Q000235:genetics; D004247:DNA / Q000378:metabolism*; D017931:DNA Primers; D015870:Gene Expression; D006609:High Mobility Group Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008067:Lipoma / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D011485:Protein Binding
D003598:Cytoskeletal Proteins; D017931:DNA Primers; D006609:High Mobility Group Proteins; D004247:DNA