Expression of a truncated Hmga1b gene induces gigantism, lipomatosis and B-cell lymphomas in mice.
HMGA1 gene rearrangements have been frequently described in human lipomas. In vitro studies suggest that HMGA1 proteins have a negative role in the control of adipocyte cell growth, and that HMGA1 gene truncation acts in a dominant-negative fashion. Therefore, to define better the role of the HMGA1 alterations in the generation of human lipomas, we generated mice carrying an Hmga1b truncated (Hmga1b/T) gene. These mice develop a giant phenotype together with a drastic expansion of the retroperitoneal and subcutaneous white adipose tissue. We show that the activation of the E2F pathway likely accounts, at least in part, for this phenotype. Interestingly, the Hmga1b/T mice also develop B-cell lymphomas similar to that occurring in Hmga1-knockout mice, supporting a dominant-negative role of the Hmga1b/T mutant also in vivo.
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Università degli Studi di Napoli Federico II, 80131 Naples, Italy.
Monica
M
Fedele
Rosa
R
Visone
Ivana
I
De Martino
Dario
D
Palmieri
Teresa
T
Valentino
Francesco
F
Esposito
Andres
A
Klein-Szanto
Claudio
C
Arra
Andrea
A
Ciarmiello
Carlo M
CM
Croce
Alfredo
A
Fusco
D017667:Adipocytes / Q000473:pathology; D000818:Animals; D049109:Cell Proliferation; D050687:E2F1 Transcription Factor / Q000378:metabolism; D005260:Female; D005877:Gigantism / Q000235:genetics*; D025742:HMGA1b Protein / Q000235:genetics* / Q000378:metabolism; D008068:Lipomatosis / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction
D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D025742:HMGA1b Protein