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Life Without White Fat - a Transgenic Mouse

  1. Author:
    Moitra, J.
    Mason, M. M.
    Olive, M.
    Krylov, D.
    Gavrilova, O.
    Marcussamuels, B.
    Feigenbaum, L.
    Lee, E.
    Aoyama, T.
    Eckhaus, M.
    Reitman, M. L.
    Vinson, C.

  2. Author Address

    Reitman ML NIDDKD DIABET BRANCH BETHESDA, MD 20892 USA NIDDKD DIABET BRANCH BETHESDA, MD 20892 USA NCI BIOCHEM LAB BETHESDA, MD 20892 USA NICHHD LAB MAMMALIAN GENES & DEV BETHESDA, MD 20892 USA NIH VET RESOURCES PROGRAM OFF RES SERV BETHESDA, MD 20892 USA NCI FREDERICK CANC RES & DEV CTR SCI APPLICAT INT CORP FREDERICK, MD 21702 USA SHINSHU UNIV SCH MED DEPT BIOCHEM MATSUMOTO NAGANO 390 JAPAN
    1. Year: 1998
  2. Journal: Genes & Development
    1. 12
    2. 20
    3. Pages: 3168-3181
  4. Type of Article: Article
  1. Abstract:

    We have generated a transgenic mouse with no white fat tissue throughout life. These mice express a dominant-negative protein, termed A-ZIP/F, under the control of the adipose-specific aP2 enhancer/promoter. This protein prevents the DNA binding of B-ZIP transcription factors of both the C/EBP and Tun families. The transgenic mice (named A-ZIP/F-1) have no white adipose tissue and dramatically reduced amounts of brown adipose tissue, which is inactive. They are initially growth delayed, but by week 12, surpass their littermates in weight. The mice eat, drink, and urinate copiously, have decreased fecundity, premature death, and frequently die after anesthesia. The physiological consequences of having no white fat tissue are profound. The liver is engorged with lipid, and the internal organs are enlarged. The mice are diabetic, with reduced leptin (20-fold) and elevated serum glucose (3-fold), insulin (50- to 400-fold), free fatty acids (2-fold), and triglycerides (3- to 5-fold). The A-ZIP/F-1 phenotype suggests a mouse model for the human disease lipoatrophic diabetes (Seip-Berardinelli syndrome), indicating that the lack of fat can cause diabetes. The myriad of consequences of having no fat throughout development can be addressed with this model. [References: 77]

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