Skip to main content

Lessons from Cre-Mice and Indicator Mice

  • Chapter
  • First Online:

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 251))

Abstract

The adult human adipose tissue is predominantly composed of white adipocytes. However, within certain depots, adipose tissue contains thermogenically active brown-like adipocytes, which have been evolutionarily conserved in mammals. This chapter will give a brief overview on the methods used to genetically target and trace both white and brown adipocytes using techniques such as bacterial artificial chromosome (BAC) cloning to create transgenic mouse models and the tools with which genetic recombination is mediated in vivo (e.g., Cre-loxP, CreERT, and Tet-On). The chapter furthermore critically discusses the strength and limitation of the various systems used to target mature white and brown adipocytes (ap2-Cre, Adipoq-Cre, and Ucp1-Cre). Based on these systems, it is evident that our knowledge of mature adipocyte categorization into brown, white, brite, or beige adipocytes is strongly influenced by the use of the various genetic mouse models described in this chapter. Our evaluation of different studies using the aforementioned systems focuses on key genes, which have been reported to maintain adipocyte’s function (insulin receptor, Raptor, or Atgl).

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Bartelt A, Bruns OT, Reimer R, Hohenberg H, Ittrich H, Peldschus K, Kaul MG, Tromsdorf UI, Weller H, Waurisch C (2011) Brown adipose tissue activity controls triglyceride clearance. Nat Med 17:200

    Article  CAS  PubMed  Google Scholar 

  • Bartelt A, Heeren J (2012) The holy grail of metabolic disease: brown adipose tissue. Curr Opin Lipidol 23:190–195

    Article  CAS  PubMed  Google Scholar 

  • Bartelt A, Heeren J (2014) Adipose tissue browning and metabolic health. Nat Rev Endocrinol 10:24

    Article  CAS  PubMed  Google Scholar 

  • Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277–359

    Article  CAS  PubMed  Google Scholar 

  • Cassard-Doulcier A-M, Gelly C, Bouillaud F, Ricquier D (1998) A 211-bp enhancer of the rat uncoupling protein-1 (UCP-1) gene controls specific and regulated expression in brown adipose tissue. Biochem J 333:243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cassard-Doulcier A-M, Gelly C, Fox N, Schrementi J, Raimbault S, Klaus S, Forest C, Bouillaud F, Ricquier D (1993) Tissue-specific and beta-adrenergic regulation of the mitochondrial uncoupling protein gene: control by cis-acting elements in the 5′-flanking region. Mol Endocrinol 7:497–506

    CAS  PubMed  Google Scholar 

  • Cohen P, Levy JD, Zhang Y, Frontini A, Kolodin DP, Svensson KJ, Lo JC, Zeng X, Ye L, Khandekar MJ (2014) Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell 156:304–316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Copeland NG, Jenkins NA (2001) Recombineering: a powerful new tool for mouse functional genomics. Nat Rev Genet 2:769

    Article  CAS  PubMed  Google Scholar 

  • Corish P, Tyler-Smith C (1999) Attenuation of green fluorescent protein half-life in mammalian cells. Protein Eng 12:1035–1040

    Article  CAS  PubMed  Google Scholar 

  • Das K, Lin Y, Widen E, Zhang Y, Scherer PE (2001) Chromosomal localization, expression pattern, and promoter analysis of the mouse gene encoding adipocyte-specific secretory protein Acrp30. Biochem Biophys Res Commun 280:1120–1129

    Article  CAS  PubMed  Google Scholar 

  • Deroo BJ, Korach KS (2006) Estrogen receptors and human disease. J Clin Invest 116:561–570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duteil D, Tosic M, Lausecker F, Nenseth HZ, Müller JM, Urban S, Willmann D, Petroll K, Messaddeq N, Arrigoni L (2016) Lsd1 ablation triggers metabolic reprogramming of brown adipose tissue. Cell Rep 17:1008–1021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eguchi J, Wang X, Yu S, Kershaw EE, Chiu PC, Dushay J, Estall JL, Klein U, Maratos-Flier E, Rosen ED (2011) Transcriptional control of adipose lipid handling by IRF4. Cell Metab 13:249–259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elmasri H, Karaaslan C, Teper Y, Ghelfi E, Weng M, Ince TA, Kozakewich H, Bischoff J, Cataltepe S (2009) Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells. FASEB J 23:3865–3873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feil R, Wagner J, Metzger D, Chambon P (1997) Regulation of Cre recombinase activity by mutated estrogen receptor ligand-binding domains. Biochem Biophys Res Commun 237:752–757

    Article  CAS  PubMed  Google Scholar 

  • Flemming W (1870) On the histogenesis of fixed cells and fat cells in connective tissue. Centrabl Med Wiss 31:481–483

    Google Scholar 

  • Fu Y, Luo N, Lopes-Virella MF (2000) Oxidized LDL induces the expression of ALBP/aP2 mRNA and protein in human THP-1 macrophages. J Lipid Res 41:2017–2023

    Article  CAS  PubMed  Google Scholar 

  • Furuhashi M, Tuncman G, Görgün CZ, Makowski L, Atsumi G, Vaillancourt E, Kono K, Babaev VR, Fazio S, Linton MF (2007) Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature 447:959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Galmozzi A, Sonne SB, Altshuler-Keylin S, Hasegawa Y, Shinoda K, Luijten IH, Chang JW, Sharp LZ, Cravatt BF, Saez E (2014) ThermoMouse: an in vivo model to identify modulators of UCP1 expression in brown adipose tissue. Cell Rep 9:1584–1593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gessner K (1551) Conradi Gesneri medici Tigurine Historiae Animalium: Lib. I De Quadrupedibus viviparis, 842

    Google Scholar 

  • Gossen M, Freundlieb S, Bender G, Muller G, Hillen W, Bujard H (1995) Transcriptional activation by tetracyclines in mammalian cells. Science 268:1766–1769

    Article  CAS  PubMed  Google Scholar 

  • Guerra C, Navarro P, Valverde AM, Arribas M, Brüning J, Kozak LP, Kahn CR, Benito M (2001) Brown adipose tissue–specific insulin receptor knockout shows diabetic phenotype without insulin resistance. J Clin Invest 108:1205–1213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harms MJ, Ishibashi J, Wang W, Lim H-W, Goyama S, Sato T, Kurokawa M, Won K-J, Seale P (2014) Prdm16 is required for the maintenance of brown adipocyte identity and function in adult mice. Cell Metab 19:593–604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hatai S (1902) On the presence in human embryos of an interscapular gland corresponding to the so-called hibernating gland of lower mammals. Anat Anz 21:369–373

    Google Scholar 

  • Hepler C, Gupta RK (2017) The expanding problem of adipose depot remodeling and postnatal adipocyte progenitor recruitment. Mol Cell Endocrinol 445:95–108

    Article  CAS  PubMed  Google Scholar 

  • Hepler C, Vishvanath L, Gupta RK (2017) Sorting out adipocyte precursors and their role in physiology and disease. Genes Dev 31:127–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Himms-Hagen J, Melnyk A, Zingaretti M, Ceresi E, Barbatelli G, Cinti S (2000) Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes. Am J Phys Cell Phys 279:C670–C681

    CAS  Google Scholar 

  • Holland WL, Xia JY, Johnson JA, Sun K, Pearson MJ, Sharma AX, Quittner-Strom E, Tippetts TS, Gordillo R, Scherer PE (2017) Inducible overexpression of adiponectin receptors highlight the roles of adiponectin-induced ceramidase signaling in lipid and glucose homeostasis. Mol Metab 6:267–275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:87–91

    Article  CAS  PubMed  Google Scholar 

  • Iwaki M, Matsuda M, Maeda N, Funahashi T, Matsuzawa Y, Makishima M, Shimomura I (2003) Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors. Diabetes 52:1655–1663

    Article  CAS  PubMed  Google Scholar 

  • Jimenez V, Muñoz S, Casana E, Mallol C, Elias I, Jambrina C, Ribera A, Ferre T, Franckhauser S, Bosch F (2013) In vivo adeno-associated viral vector–mediated genetic engineering of white and brown adipose tissue in adult mice. Diabetes 62:4012–4022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jo J, Gavrilova O, Pack S, Jou W, Mullen S, Sumner AE, Cushman SW, Periwal V (2009) Hypertrophy and/or hyperplasia: dynamics of adipose tissue growth. PLoS Comput Biol 5:e1000324

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Johansson T, Broll I, Frenz T, Hemmers S, Becher B, Zeilhofer HU, Buch T (2010) Building a zoo of mice for genetic analyses: a comprehensive protocol for the rapid generation of BAC transgenic mice. Genesis 48:264–280

    Article  CAS  PubMed  Google Scholar 

  • Johnson P, Hirsch J (1972) Cellularity of adipose depots in six strains of genetically obese mice. J Lipid Res 13:2–11

    Article  CAS  PubMed  Google Scholar 

  • Jopling C, Boue S, Belmonte JCI (2011) Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration. Nat Rev Mol Cell Biol 12:79

    Article  CAS  PubMed  Google Scholar 

  • Kahn SE, Hull RL, Utzschneider KM (2006) Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444:840

    Article  CAS  PubMed  Google Scholar 

  • Kim HB, Kong M, Kim TM, Suh YH, Kim W-H, Lim JH, Song JH, Jung MH (2006) NFATc4 and ATF3 negatively regulate adiponectin gene expression in 3T3-L1 adipocytes. Diabetes 55:1342–1352

    Article  CAS  PubMed  Google Scholar 

  • Kong X, Banks A, Liu T, Kazak L, Rao RR, Cohen P, Wang X, Yu S, Lo JC, Tseng Y-H (2014) IRF4 is a key thermogenic transcriptional partner of PGC-1α. Cell 158:69–83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krishnan J, Danzer C, Simka T, Ukropec J, Walter KM, Kumpf S, Mirtschink P, Ukropcova B, Gasperikova D, Pedrazzini T (2012) Dietary obesity-associated Hif1α activation in adipocytes restricts fatty acid oxidation and energy expenditure via suppression of the Sirt2-NAD+ system. Genes Dev 26:259–270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krombach F, Münzing S, Allmeling A-M, Gerlach JT, Behr J, Dörger M (1997) Cell size of alveolar macrophages: an interspecies comparison. Environ Health Perspect 105:1261

    PubMed  PubMed Central  Google Scholar 

  • Labbé SM, Mouchiroud M, Caron A, Secco B, Freinkman E, Lamoureux G, Gélinas Y, Lecomte R, Bossé Y, Chimin P (2016) mTORC1 is required for brown adipose tissue recruitment and metabolic adaptation to cold. Sci Rep 6:37223

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lasar D, Rosenwald M, Kiehlmann E, Balaz M, Tall B, Opitz L, Lidell ME, Zamboni N, Krznar P, Sun W (2018) Peroxisome proliferator activated receptor gamma controls mature brown adipocyte inducibility through glycerol kinase. Cell Rep 22:760–773

    Article  CAS  PubMed  Google Scholar 

  • Lee MY, Tse H-F, Siu C-W, Zhu S-G, Man RY, Vanhoutte PM (2007) Genomic changes in regenerated porcine coronary arterial endothelial cells. Arterioscler Thromb Vasc Biol 27:2443–2449

    Article  CAS  PubMed  Google Scholar 

  • Lee PL, Tang Y, Li H, Guertin DA (2016) Raptor/mTORC1 loss in adipocytes causes progressive lipodystrophy and fatty liver disease. Mol Metab 5:422–432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee Y-K, Cowan CA (2013) White to brite adipocyte transition and back again. Nat Cell Biol 15:568

    Article  CAS  PubMed  Google Scholar 

  • Liu P, Ji Y, Yuen T, Rendina-Ruedy E, DeMambro VE, Dhawan S, Abu-Amer W, Izadmehr S, Zhou B, Shin AC (2017) Blocking FSH induces thermogenic adipose tissue and reduces body fat. Nature 546:107–112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Makowski L, Boord JB, Maeda K, Babaev VR, Uysal KT, Morgan MA, Parker RA, Suttles J, Fazio S, Hotamisligil GS (2001) Lack of macrophage fatty-acid–binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nat Med 7:699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mao L, Nie B, Nie T, Hui X, Gao X, Lin X, Liu X, Xu Y, Tang X, Yuan R (2017) Visualization and quantification of browning using a Ucp1-2A-Luciferase knock-in mouse model. Diabetes 66:407–417

    Article  CAS  PubMed  Google Scholar 

  • Mitsui Y, Schneider EL (1976) Relationship between cell replication and volume in senescent human diploid fibroblasts. Mech Ageing Dev 5:45–56

    Article  CAS  PubMed  Google Scholar 

  • Moulin K, Truel N, André M, Arnauld E, Nibbelink M, Cousin B, Dani C, Pénicaud L, Casteilla L (2001) Emergence during development of the white-adipocyte cell phenotype is independent of the brown-adipocyte cell phenotype. Biochem J 356:659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moullan N, Mouchiroud L, Wang X, Ryu D, Williams EG, Mottis A, Jovaisaite V, Frochaux MV, Quiros PM, Deplancke B (2015) Tetracyclines disturb mitochondrial function across eukaryotic models: a call for caution in biomedical research. Cell Rep 10:1681–1691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Müller S, Kulenkampff E, Wolfrum C (2015) Adipose tissue stem cells. Metabolic control. Springer, Berlin, pp 251–263

    Google Scholar 

  • O’Neill SM, Hinkle C, Chen S-J, Sandhu A, Hovhannisyan R, Stephan S, Lagor WR, Ahima RS, Johnston JC, Reilly MP (2014) Targeting adipose tissue via systemic gene therapy. Gene Ther 21:653

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Orban PC, Chui D, Marth JD (1992) Tissue-and site-specific DNA recombination in transgenic mice. Proc Natl Acad Sci U S A 89:6861–6865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Osoegawa K, Tateno M, Woon PY, Frengen E, Mammoser AG, Catanese JJ, Hayashizaki Y, de Jong PJ (2000) Bacterial artificial chromosome libraries for mouse sequencing and functional analysis. Genome Res 10:116–128

    CAS  PubMed  PubMed Central  Google Scholar 

  • Park S-K, Oh S-Y, Lee M-Y, Yoon S, Kim K-S, Kim J-W (2004) CCAAT/enhancer binding protein and nuclear factor-Y regulate adiponectin gene expression in adipose tissue. Diabetes 53:2757–2766

    Article  CAS  PubMed  Google Scholar 

  • Qiang G, Kong HW, Xu S, Pham HA, Parlee SD, Burr AA, Gil V, Pang J, Hughes A, Gu X (2016) Lipodystrophy and severe metabolic dysfunction in mice with adipose tissue-specific insulin receptor ablation. Mol Metab 5:480–490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rajakumari S, Wu J, Ishibashi J, Lim H-W, Giang A-H, Won K-J, Reed RR, Seale P (2013) EBF2 determines and maintains brown adipocyte identity. Cell Metab 17:562–574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rajewsky K, Gu H, Kühn R, Betz UA, Müller W, Roes J, Schwenk F (1996) Conditional gene targeting. J Clin Invest 98:600–603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rickert RC, Roes J, Rajewsky K (1997) B lymphocyte-specific, Cre-mediated mutagenesis in mice. Nucleic Acids Res 25:1317–1318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosengren S, Henson PM, Worthen GS (1994) Migration-associated volume changes in neutrophils facilitate the migratory process in vitro. Am J Phys Cell Phys 267:C1623–C1632

    CAS  Google Scholar 

  • Rosenwald M, Perdikari A, Rülicke T, Wolfrum C (2013) Bi-directional interconversion of brite and white adipocytes. Nat Cell Biol 15:659

    Article  CAS  PubMed  Google Scholar 

  • Sakaguchi M, Fujisaka S, Cai W, Winnay JN, Konishi M, O’Neill BT, Li M, García-Martín R, Takahashi H, Hu J (2017) Adipocyte dynamics and reversible metabolic syndrome in mice with an inducible adipocyte-specific deletion of the insulin receptor. Cell Metab 25:448–462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sambeat A, Gulyaeva O, Dempersmier J, Tharp KM, Stahl A, Paul SM, Sul HS (2016) LSD1 interacts with Zfp516 to promote UCP1 transcription and brown fat program. Cell Rep 15:2536–2549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanchez-Gurmaches J, Guertin DA (2014) Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed. Nat Commun 5:4099

    Article  CAS  PubMed  Google Scholar 

  • Sanchez-Gurmaches J, Hung C-M, Sparks CA, Tang Y, Li H, Guertin DA (2012) PTEN loss in the Myf5 lineage redistributes body fat and reveals subsets of white adipocytes that arise from Myf5 precursors. Cell Metab 16:348–362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanchez-Gurmaches J, Tang Y, Jespersen NZ, Wallace M, Calejman CM, Gujja S, Li H, Edwards YJ, Wolfrum C, Metallo CM (2018) Brown fat AKT2 is a cold-induced kinase that stimulates ChREBP-mediated de Novo lipogenesis to optimize fuel storage and thermogenesis. Cell Metab 27:195–209.e6

    Article  CAS  PubMed  Google Scholar 

  • Schmid-Schonbein G, Shih YY, Chien S (1980) Morphometry of human leukocytes. Blood 56:866–875

    Article  CAS  PubMed  Google Scholar 

  • Schreiber R, Diwoky C, Schoiswohl G, Feiler U, Wongsiriroj N, Abdellatif M, Kolb D, Hoeks J, Kershaw EE, Sedej S (2017) Cold-induced thermogenesis depends on ATGL-mediated lipolysis in cardiac muscle, but not brown adipose tissue. Cell Metab 26:753–763.e7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Segawa K, Matsuda M, Fukuhara A, Morita K, Okuno Y, Komuro R, Shimomura I (2009) Identification of a novel distal enhancer in human adiponectin gene. J Endocrinol 200:107–116

    Article  CAS  PubMed  Google Scholar 

  • Shan T, Liu W, Kuang S (2013) Fatty acid binding protein 4 expression marks a population of adipocyte progenitors in white and brown adipose tissues. FASEB J 27:277–287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shao M, Ishibashi J, Kusminski CM, Wang QA, Hepler C, Vishvanath L, MacPherson KA, Spurgin SB, Sun K, Holland WL (2016) Zfp423 maintains white adipocyte identity through suppression of the beige cell thermogenic gene program. Cell Metab 23:1167–1184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shaw HB (1901) A contribution to the study of the morphology of adipose tissue. J Anat Physiol 36:1

    CAS  PubMed  PubMed Central  Google Scholar 

  • Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Näslund E, Britton T (2008) Dynamics of fat cell turnover in humans. Nature 453:783

    Article  CAS  PubMed  Google Scholar 

  • Sternberg N, Hamilton D (1981) Bacteriophage P1 site-specific recombination: I. Recombination between loxP sites. J Mol Biol 150:467–486

    Article  CAS  PubMed  Google Scholar 

  • Sun K, Kusminski CM, Luby-Phelps K, Spurgin SB, An YA, Wang QA, Holland WL, Scherer PE (2014) Brown adipose tissue derived VEGF-A modulates cold tolerance and energy expenditure. Mol Metab 3:474–483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Turpin SM, Nicholls HT, Willmes DM, Mourier A, Brodesser S, Wunderlich CM, Mauer J, Xu E, Hammerschmidt P, Brönneke HS (2014) Obesity-induced CerS6-dependent C 16: 0 ceramide production promotes weight gain and glucose intolerance. Cell Metab 20:678–686

    Article  CAS  PubMed  Google Scholar 

  • Urs S, Harrington A, Liaw L, Small D (2006) Selective expression of an aP2/fatty acid binding Protein4-Cre transgene in non-adipogenic tissues during embryonic development. Transgenic Res 15:647–653

    Article  CAS  PubMed  Google Scholar 

  • Vitali A, Murano I, Zingaretti MC, Frontini A, Ricquier D, Cinti S (2012) The adipose organ of obesity-prone C57BL/6J mice is composed of mixed white and brown adipocytes. J Lipid Res 53:619–629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang QA, Scherer PE (2014) The AdipoChaser mouse: a model tracking adipogenesis in vivo. Adipocytes 3:146–150

    Article  CAS  Google Scholar 

  • Wang QA, Scherer PE, Gupta RK (2014) Improved methodologies for the study of adipose biology: insights gained and opportunities ahead. J Lipid Res 55:605–624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang QA, Tao C, Gupta RK, Scherer PE (2013) Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat Med 19:1338

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang ZV, Deng Y, Wang QA, Sun K, Scherer PE (2010) Identification and characterization of a promoter cassette conferring adipocyte-specific gene expression. Endocrinology 151:2933–2939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Warming S, Costantino N, Court DL, Jenkins NA, Copeland NG (2005) Simple and highly efficient BAC recombineering using galK selection. Nucleic Acids Res 33:e36

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Widdowson EM (1976) The response of the sexes to nutritional stress. Proc Nutr Soc 35:175–180

    Article  CAS  PubMed  Google Scholar 

  • Xia JY, Sun K, Hepler C, Ghaben AL, Gupta RK, An YA, Holland WL, Morley TS, Adams AC, Gordillo R (2017) Acute loss of adipose tissue-derived adiponectin triggers immediate metabolic deterioration in mice. Diabetologia:1–10

    Google Scholar 

  • Yang M, Baranov E, Jiang P, Sun F-X, Li X-M, Li L, Hasegawa S, Bouvet M, Al-Tuwaijri M, Chishima T (2000) Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases. Proc Natl Acad Sci 97:1206–1211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye R, Wang QA, Tao C, Vishvanath L, Shao M, McDonald JG, Gupta RK, Scherer PE (2015) Impact of tamoxifen on adipocyte lineage tracing: inducer of adipogenesis and prolonged nuclear translocation of Cre recombinase. Mol Metab 4:771–778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang F, Hao G, Shao M, Nham K, An Y, Wang Q, Zhu Y, Kusminski CM, Hassan G, Gupta RK (2018) An adipose tissue atlas: an image-guided identification of human-like BAT and beige depots in rodents. Cell Metab 27:252–262.e3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu Y, Gao Y, Tao C, Shao M, Zhao S, Huang W, Yao T, Johnson JA, Liu T, Cypess AM (2016) Connexin 43 mediates white adipose tissue beiging by facilitating the propagation of sympathetic neuronal signals. Cell Metab 24:420–433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Leon Gabriel Straub .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Wolfrum, C., Straub, L.G. (2018). Lessons from Cre-Mice and Indicator Mice. In: Pfeifer, A., Klingenspor, M., Herzig, S. (eds) Brown Adipose Tissue. Handbook of Experimental Pharmacology, vol 251. Springer, Cham. https://doi.org/10.1007/164_2018_146

Download citation

Publish with us

Policies and ethics