Life without white fat: a transgenic mouse

• Published in: Genes & development 1998-10, Vol.12 (20), p.3168-3181
• Main Authors: Moitra, J, Mason, M M, Olive, M, Krylov, D, Gavrilova, O, Marcus-Samuels, B, Feigenbaum, L, Lee, E, Aoyama, T, Eckhaus, M, Reitman, M L, Vinson, C
• Format: Article
• Language: English
• Subjects: Adipose Tissue - abnormalities; Adipose Tissue, Brown - pathology; Amino Acid Sequence; Animals; CCAAT-Enhancer-Binding Proteins; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - mortality; Diabetes Mellitus, Experimental - pathology; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - metabolism; Fasting; Female; Leptin; Leucine Zippers - genetics; Male; Mice; Mice, Transgenic - genetics; Mice, Transgenic - growth & development; Mice, Transgenic - metabolism; Molecular Sequence Data; Nuclear Proteins - antagonists & inhibitors; Nuclear Proteins - metabolism; Phenotype; Proteins - genetics; Research Paper; RNA, Messenger - biosynthesis; Transcription Factor AP-1 - antagonists & inhibitors; Transcription Factor AP-1 - metabolism; Viscera - pathology
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.12.20.3168

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 Jun 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.