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.

• Publication year

  2000

• Venue

  Journal of Biological Chemistry

• Publication date

  2000-05-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.M000564200PMID 10747931
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• High-mobility-group proteins and cancer—an emerging link

  2005cited by this paper
• The expression of a truncated HMGI-C gene induces gigantism associated with lipomatosis.

  1999cited by this paper
• A Novel, Multifunctional c-Cbl Binding Protein in Insulin Receptor Signaling in 3T3-L1 Adipocytes

  1998cited by this paper
• Truncated and chimeric HMGI-C genes induce neoplastic transformation of NIH3T3 murine fibroblasts

  1998cited by this paper
• Identification of NFIB as recurrent translocation partner gene of HMGIC in pleomorphic adenomas

  1998cited by this paper
• Efficient recruitment of TFIIB and CBP-RNA polymerase II holoenzyme by an interferon-beta enhanceosome in vitro.

  1998cited by this paper
• Chromatin remodeling of the interleukin-2 gene: distinct alterations in the proximal versus distal enhancer regions.

  1998cited by this paper
• Thiazolidinediones and insulin resistance: peroxisome proliferatoractivated receptor gamma activation stimulates expression of the CAP gene.

  1998cited by this paper
• A role for the architectural transcription factors HMGI(Y) in cytokine gene transcription in T cells

  1998cited by this paper
• Genetic instabilities in human cancers

  1998cited by this paper
• Molecules in focus The high mobility group protein, HMGI-C

  1998cited by this paper
• The high mobility group protein, HMGI-C.

  1998cited by this paper
• A novel, multifuntional c-Cbl binding protein in insulin receptor signaling in 3T3-L1 adipocytes.

  1998cited by this paper
• High mobility group I/Y protein functions as a specific cofactor for Oct‐2A: mapping of interaction domains

  1998cited by this paper
• Intra- and intermolecular cooperative binding of high-mobility-group protein I(Y) to the beta-interferon promoter

  1997cited by this paper
• The mechanism of transcriptional synergy of an in vitro assembled interferon-beta enhanceosome.

  1997cited by this paper
• High Mobility Group I Proteins Interfere with the Homeodomains Binding to DNA*

  1997cited by this paper
• Expression of HMGI-C and HMGI(Y) in ordinary lipoma and atypical lipomatous tumors: immunohistochemical reactivity correlates with karyotypic alterations.

  1997cited by this paper
• Human colorectal carcinomas express high levels of high mobility group HMGI(Y) proteins.

  1996cited by this paper
• Spontaneous Lesions in Aging FVB/N Mice

  1996cited by this paper
• High-mobility-group chromosomal proteins: architectural components that facilitate chromatin function.

  1996cited by this paper
• HMGI-C expression patterns in human tissues. Implications for the genesis of frequent mesenchymal tumors.

  1996cited by this paper
• Reversal of intrinsic DNA bends in the IFN beta gene enhancer by transcription factors and the architectural protein HMG I(Y).

  1995cited by this paper
• Mutation responsible for the mouse pygmy phenotype in the developmentally regulated factor HMGI-C

  1995cited by this paper
• Recurrent rearrangements in the high mobility group protein gene, HMGI-C, in benign mesenchymal tumours

  1995cited by this paper
• Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y), and NF-kappa B family proteins

  1995cited by this paper
• The gene for the human architectural transcription factor HMGI-C consists of five exons each coding for a distinct functional element.

  1995cited by this paper
• Disruption of the architectural factor HMGI-C: DNA-binding AT hook motifs fused in lipomas to distinct transcriptional regulatory domains.

  1995cited by this paper
• Molecular characterization of 12q14-15 rearrangements in three pulmonary chondroid hamartomas.

  1995cited by this paper
• Functional interaction between the POU domain protein Tst-1/Oct-6 and the high-mobility-group protein HMG-I/Y

  1995cited by this paper
• The expression of the high mobility group HMGI (Y) proteins correlates with the malignant phenotype of human thyroid neoplasias.

  1995cited by this paper
• Functional roles of the transcription factor Oct-2A and the high mobility group protein I/Y in HLA-DRA gene expression

  1995cited by this paper
• Short peptide fragments derived from HMG-I/Y proteins bind specifically to the minor groove of DNA.

  1994cited by this paper
• Cooperativity between two NF-kappa B complexes, mediated by high-mobility-group protein I(Y), is essential for cytokine-induced expression of the E-selectin promoter.

  1994cited by this paper
• Metaphase chromosome structure: bands arise from a differential folding path of the highly AT-rich scaffold.

  1994cited by this paper
• Mechanisms of transcriptional synergism between distinct virus-inducible enhancer elements.

  1993cited by this paper
• The high mobility group protein HMG I(Y) is an essential structural component of a virus-inducible enhancer complex.

  1993cited by this paper
• SAR‐dependent mobilization of histone H1 by HMG‐I/Y in vitro: HMG‐I/Y is enriched in H1‐depleted chromatin.

  1993cited by this paper
• High-mobility-group (HMG) proteins and histone H1 subtypes expression in normal and tumor tissues of mouse.

  1993cited by this paper
• The high mobility group protein HMG I(Y) is required for NF-kappa B-dependent virus induction of the human IFN-beta gene.

  1992cited by this paper
• The High Mobility Group protein HMG I(Y) is required for NF-κB-dependent virus induction of the human IFN-β gene

  1992cited by this paper
• Transgenic mouse model for central nervous system demyelination

  1991cited by this paper
• Protein motifs that recognize structural features of DNA.

  1991cited by this paper
• cDNA cloning of the HMGI-C phosphoprotein, a nuclear protein associated with neoplastic and undifferentiated phenotypes.

  1991cited by this paper
• The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure.

  1990cited by this paper
• Analysis of the HMGI nuclear proteins in mouse neoplastic cells induced by different procedures.

  1989cited by this paper
• Structure of mouse fatty acid synthase mRNA. Identification of the two NADPH binding sites.

  1989cited by this paper
• Complete murine cDNA sequence, genomic structure, and tissue expression of the high mobility group protein HMG-I(Y).

  1988cited by this paper
• Elevated levels of a specific class of nuclear phosphoproteins in cells transformed with v‐ras and v‐mos oncogenes and by cotransfection with c‐myc and polyoma middle T genes.

  1987cited by this paper
• Regulated expression of a murine class I gene in transgenic mice

  1986cited by this paper
• Factors affecting the efficiency of introducing foreign DNA into mice by microinjecting eggs.

  1985cited by this paper
• Pathologic Basis of Disease

  1974cited by this paper

• Syndrome Associated Lipomatous Tumors (SALT): A Comprehensive Review.

  2026cites this paper
• Molecular Genetics and Epigenetics Regulatory Role of miRNAs on Adipogenesis and Intramuscular Fat Development in Beef Cattle: In the Context of Meat Quality.

  2025cites this paper
• Lipomas are associated with a higher prevalence of metabolic syndrome components: a multicenter cross-sectional study

  2025cites this paper
• Uterine Fibroids.

  2025cites this paper
• High Mobility Group A1 Chromatin Keys: Unlocking the Genome During MPN Progression

  2025cites this paper
• Inhibition of HMGA2 binding to AT-rich DNA by its negatively charged C-terminus

  2025cites this paper
• The Transcriptomic and Gene Fusion Landscape of Pleomorphic Salivary Gland Adenomas

  2025cites this paper
• A rare case of pelvic lipomatososis in a cadaveric renal transplant recipient

  2024cites this paper
• Diagnostic and Predictive Immunocytochemistry in Head and Neck Lesions

  2024cites this paper
• Presence of a t(12;18)(q14;q21) Chromosome Translocation and Fusion of the Genes for High-mobility Group AT-Hook 2 (HMGA2) and WNT Inhibitory Factor 1 (WIF1) in Infrapatellar Fat Pad Cells from a Patient With Hoffa’s Disease

  2022cites this paper
• Neoplasia-associated Chromosome Translocations Resulting in Gene Truncation

  2022cites this paper
• The role of HMGA1 protein in gastroenteropancreatic neuroendocrine tumors

  2022cites this paper
• Chromosomal Translocation t(5;12)(p13;q14) Leading to Fusion of High-mobility Group AT-hook 2 Gene With Intergenic Sequences From Chromosome Sub-Band 5p13.2 in Benign Myoid Neoplasms of the Breast: A Second Case

  2022cites this paper
• Recurrent Fusion of the Genes for High-mobility Group AT-hook 2 (HMGA2) and Nuclear Receptor Co-repressor 2 (NCOR2) in Osteoclastic Giant Cell-rich Tumors of Bone

  2022cites this paper
• Analysis of the miRNA expression from the adipose tissue surrounding the adrenal neoplasia

  2022cites this paper
• Fusion of High Mobility Group AT-hook 2 Gene (HMGA2) With the Chromosome 12 Open Reading Frame 42 Gene (C12orf42) in an Aggressive Angiomyxoma With del(12)(q14q23) as the Sole Cytogenetic Anomaly

  2022cites this paper
• 3’ UTR-truncated HMGA2 overexpression induces non-malignant in vivo expansion of hematopoietic stem cells in non-human primates

  2021cites this paper
• MicroRNA Expression Profiles in the Subcutaneous Adipose Tissues of Morbidly Obese Chinese Women

  2021cites this paper
• Critical role of the high mobility group A proteins in hematological malignancies

  2021cites this paper
• An RNAi Screening of Clinically Relevant Transcription Factors Regulating Human Adipogenesis and Adipocyte Metabolism

  2021cites this paper
• The protective effects of HMGA2 in the senescence process of bone marrow‐derived mesenchymal stromal cells

  2020cites this paper
• High Mobility Group AT-Hook 2 (HMGA2) Oncogenicity in Mesenchymal and Epithelial Neoplasia

  2020cites this paper
• HMGA Genes and Proteins in Development and Evolution

  2020cites this paper
• The Mammalian High Mobility Group Protein AT-Hook 2 (HMGA2): Biochemical and Biophysical Properties, and Its Association with Adipogenesis

  2020cites this paper
• Die Rolle der HMGA-Proteine („high mobility group AT-hook“) bei Proliferation und Differenzierung mesenchymaler Zellen und Gewebe

  2020cites this paper
• HMGA Proteins in Stemness and Differentiation of Embryonic and Adult Stem Cells

  2020cites this paper
• A review of retroperitoneal liposarcoma genomics.

  2020cites this paper
• FOS-ANKH and FOS-RUNX2 Fusion Genes in Osteoblastoma

  2020cites this paper
• Interplay between HMGA and TP53 in cell cycle control along tumor progression

  2020cites this paper
• High HMGA2 expression without gene rearrangement in meningiomas

  2020cites this paper
• Pseudoacromegaly.

  2019cites this paper
• Emerging Role of USP8, HMGA, and Non-Coding RNAs in Pituitary Tumorigenesis

  2019cites this paper
• Lessons from the Crypt: HMGA1-Amping up Wnt for Stem Cells and Tumor Progression.

  2018cites this paper
• Insights and Implications of Genome-Wide Association Studies of Height

  2018cites this paper
• HMGA2 promotes intestinal tumorigenesis by facilitating MDM2‐mediated ubiquitination and degradation of p53

  2018cites this paper
• HMGA2 (high mobility group AT-hook 2)

  2018cites this paper
• The Roles of Insulin-Like Growth Factor 2 mRNA-Binding Protein 2 in Cancer and Cancer Stem Cells

  2018cites this paper
• Suppression of HMGA2 protein synthesis could be a tool for the therapy of well differentiated liposarcomas overexpressing HMGA2.

  2018cites this paper
• A Research of Soft Tissue Lipoma Genesis Factor With Immunohistochemical Analysis

  2017cites this paper
• Animal Models of Paroxysmal Nocturnal Hemoglobinuria

  2017cites this paper
• Laser-Assisted Soft Tissue Oral Surgery: Benign Soft Tissue Lesions and Pre-prosthodontic Procedures

  2017cites this paper
• Gene fusions in soft tissue tumors: Recurrent and overlapping pathogenetic themes

  2016influential citation
• SREBP-1c/MicroRNA 33b Genomic Loci Control Adipocyte Differentiation

  2016cites this paper
• The recurrent chromosomal translocation t(12;18) (q14~15;q12~21) causes the fusion gene HMGA2-SETBP1 and HMGA2 expression in lipoma and osteochondrolipoma

  2015cites this paper
• Soft Tissue Tumors

  2015cites this paper
• Epidemiological and genetic clues for molecular mechanisms involved in uterine leiomyoma development and growth.

  2015cites this paper
• Étude génomique et fonctionnelle de la dérégulation du gène HMGA2 dans les tumeurs adipocytaires

  2015cites this paper
• TARGETING THE MDM2-P53 AXIS FOR THE TREATMENT OF DEDIFFERENTIATED LIPOSARCOMA

  2014cites this paper
• Regulation of Adipocyte Differentiation via MicroRNAs

  2014cites this paper
• Hmga1/Hmga2 double knock-out mice display a “superpygmy” phenotype

  2014cites this paper
• HMGB1 in health and disease.

  2014cites this paper
• A conditional system to specifically link disruption of protein-coding function with reporter expression in mice.

  2014cites this paper
• Identification of PPAP 2 B as a Novel Recurrent Translocation Partner Gene of HMGA 2 in Lipomas

  2013cites this paper
• HMGA2 and high-grade serous ovarian carcinoma

  2013cites this paper
• The HMGA1 protoncogene frequently deregulated in cancer is a transcriptional target of E2F1

  2013cites this paper
• Establishment and optimization of induced pluripotent stem cell technologies.

  2013cites this paper
• Identification of genes regulated by CBX7 protein and characterization of the transcriptional regulation mechanism of the SPP1 gene

  2013cites this paper
• Identification of PPAP2B as a novel recurrent translocation partner gene of HMGA2 in lipomas

  2013cites this paper
• The High Mobility Group A proteins contribute to thyroid cell transformation by regulating miR‐603 and miR‐10b expression

  2013cites this paper
• Probing into the Biological Processes Influenced by ESC Factor and Oncoprotein HMGA2 Using iPSCs

  2012cites this paper
• Rearrangement of HMGA2 in a case of infantile lipoblastoma without Plag1 alteration

  2012cites this paper
• HMGA gene rearrangement is a recurrent somatic alteration in polypoid endometriosis.

  2012cites this paper
• Pelvic Lipomatosis: A Rare Case with a Good Surgical Outcome

  2012cites this paper
• Vulval Lipoma.. A Rare Site

  2011cites this paper
• Isolated GH deficiency: mutation screening and copy number analysis of HMGA2 and CDK6 genes.

  2011cites this paper
• AKNA: Another AT-hook transcription factor “hooking-up” with inflammation

  2011cites this paper
• The response of HMGA1 to changes in oxygen availability is evolutionarily conserved.

  2011cites this paper
• HMGA2 (high mobility group AT-hook 2)

  2011cites this paper
• 3'UTR-truncated Hmga2 cDNA causes MPN-like hematopoiesis by conferring a clonal growth advantage at the level of HSC in mice.

  2011cites this paper
• Expression of a truncated Hmga1b gene induces gigantism, lipomatosis and B-cell lymphomas in mice.

  2011cites this paper
• HMGIC (high mobility group protein isoform I-C)

  2011cites this paper
• MicroRNAs in adipogenesis and as therapeutic targets for obesity

  2011cites this paper
• Overexpression of HMGA2 Promotes Metastasis and Impacts Survival of Colorectal Cancers

  2011cites this paper
• Identification of a New Pathway for Tumor Progression: MicroRNA-181b Up-Regulation and CBX7 Down-Regulation by HMGA1 Protein.

  2010cites this paper
• HMGA1 and HMGA2 rearrangements in mass‐forming endometriosis

  2010cites this paper
• Fusion of HMGA2 to COG5 in uterine leiomyoma.

  2010cites this paper
• Role of the high mobility group A proteins in the regulation of pituitary cell cycle.

  2010cites this paper
• In vivo modulation of HMGA2 expression.

  2010cites this paper
• HMGA2: A pituitary tumour subtype-specific oncogene?

  2010cites this paper
• HMGA and cancer.

  2010cites this paper
• Value and limitation of immunohistochemical expression of HMGA2 in mesenchymal tumors: about a series of 1052 cases

  2010cites this paper
• 23. Soft Tissue Tumors

  2010cites this paper
• Liposarcoma: Molecular Genetics and Therapeutics

  2010cites this paper
• Encephalocraniocutaneous lipomatosis (ECCL) in a patient with history of familial multiple lipomatosis (FML)

  2009cites this paper
• Interaction between HMGA1 and Retinoblastoma Protein Is Required for Adipocyte Differentiation*

  2009cites this paper
• MicroRNA let-7 regulates 3T3-L1 adipogenesis.

  2009cites this paper
• HMGA 2 Participates in Transformation in Human Lung Cancer

  2008cites this paper
• The HMGA proteins: a myriad of functions (Review).

  2008cites this paper
• HMGA2 Participates in Transformation in Human Lung Cancer

  2008cites this paper
• Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf Expression.

  2008cites this paper
• Regulation of Lymphocyte Function by PPARγ: Relevance to Thyroid Eye Disease-Related Inflammation

  2008cites this paper
• A crucial role of a high mobility group protein HMGA2 in cardiogenesis

  2008cites this paper
• HMGA2 is the partner of MDM2 in well‐differentiated and dedifferentiated liposarcomas whereas CDK4 belongs to a distinct inconsistent amplicon

  2008cites this paper
• Familial multiple lipomatosis: report of a new family.

  2007cites this paper
• Transcriptional regulation by targeted expression of architectural transcription factor high mobility group A2 in salivary glands of transgenic mice.

  2007cites this paper
• HMGA2 overexpression in non‐small cell lung cancer

  2007cites this paper
• WIF1, an inhibitor of the Wnt pathway, is rearranged in salivary gland tumors

  2007cites this paper
• Oncogenic HMGA2: short or small?

  2007cites this paper
• Roles of HMGA proteins in cancer

  2007cites this paper
• Frequency and characterization of HMGA2 and HMGA1 rearrangements in mesenchymal tumors of the lower genital tract

  2007cites this paper