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The following is the latest addition to the Genetically Modified Animals in Endocrinology Bibliography Project. To see earlier segments of this project, go to http://www.endo-society.org/journals/bibliographies.cfm. Please send your comments, suggestions, and offerings of other relevant citations to this e-mail address: ERKO{at}endo-society.org.
Transgenic (Tg) and Gene Knockout (KO) Models that Effect Energy Balance and/or Body Composition1
I. RECEPTORS/TRANSPORTERS
2-Adrenergic
Valet P, Grujic D, Wade J, Ito M, Zingaretti MC, Soleveva V, Ross SR, Graves RA, Cinti S, Lafontan M, Lowell BB 2000 Expression of human 2-adrenergic receptors in adipose tissue of ß3-adrenergic receptor-deficient mice promotes diet-induced obesity. J Biol Chem 275:34797–34802
ß-Adrenergic
Bachman ES, Dhillon H, Zhang CY, Cinti S, Bianco AC, Kobilka BK, Lowell BB 2002 ß-AR signaling required for diet induced thermogenesis and obesity resistance. Science 297:843–845
Bombesin BRS-3
Ohki-Hamazaki H, Watase K, Yamamoto K, Ogura H, Yamano M, Yamada K, Maeno H, Imaki J, Kikuyama S, Wada E, Wada K 1997 Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity. Nature 390:165–169[CrossRef][Medline]
Cannabinoid CB1 R
Raviet-Trillou C, Delgorge C, Menet C, Arnone M, Soubrie P 2004 CB1 Cannabinoid receptor knockout in mice leads to leanness, resistance to diet-induced obesity and enhanced leptin sensitivity. Int J Obes Relat Disord 28:640–648
CCKA
Fumakoshi A, Miyassaka K, Shinozaki H, Masada M, Kawanami T, Takata Y, Komo A 1993 An animal model of congenital defect of gene expression of cholecystokinin (CCK)-A receptor. Biochem Biophy Res Commun 210:787–796
Dopamine D1/D2
Zhou QY, Palmiter RD 1995 Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic. Cell 83:1197–1209[CrossRef][Medline]
Drago J, Gerfen CR, Lachowicz JE, Steiner H, Hollon TR, Love PE, Ooi GT, Grinberg A, Lee EJ, Huang SP, Bartlett PF, Jose PA, Sibley DR, Westphal H 1994 Altered striatal function in a mutant mouse lacking D1A dopamine receptors. Proc Natl Acad Sci USA 91:12564–12568
Xu M, Moratalla R, Gold LH, Hiroi N, Koob GF, Graybiel AM, Tonegawa S 1994 Dopamine D1 receptor mutant mice are deficient in striatal expression of dynorphin and in dopamine-mediated behavioral responses. Cell 79:729–742[CrossRef][Medline]
Dopamine D3R
Benoit SC, McQuade JA, Clegg DJ, Xu M, Rushing PA, Woods SC, Seeley RJ 2003 Altered feeding responses in mice with targeted disruption of the dopamine-3 receptor gene. Behav Neurosci 117:46–54[CrossRef][Medline]
Estrogen R
Heine PA, Taylor JA, Iwamoto GA, Lubahn DB, Cooke PS 2000 Increased adipose tissue in male and female estrogen receptor-knockout mice. Proc Natl Acad Sci USA 97:12729–12734
FSH-R
Danilovich N, Babu PS, Xing W, Gerdes M, Krishnamurthy H, Sairam MR 2000 Estrogen deficiency, obesity, and skeletal abnormalities in FSH receptor knockout (FORKO) female mice. Endocrinology 141:4295–4308
GABA Transporter I
Ma YH, Zhou XG, Zeng RW, Mei ZT, Fei J, Guo LH 2000 Transgenic mice overexpressing 
-aminobutyric acid transporter subtype I develop obesity. Cell Res 10: 303–310[CrossRef][Medline]
GRII
Pepin M-C, Barden N 1991 Decreased glucocorticoid receptor activity following glucocorticoid receptor antisense RNA gene fragment transfection. Mol Cell Biol 11:1647–1653
Richard D, Chapdelaine S, Deshaies Y, Pepin M-C, Barden N 1993 Energy balance and lipid metabolism in transgenic mice bearing an antisense GCR gene construct. Am J Physiol 265:R146–R150[Medline]
Histamine H1
Masaki T, Yoshimatsu H, Chiba S, Watanabe T, Sakata T 2001 Targeted disruption of histamine H1-receptor attenuates regulatory effects of leptin on feeding, adiposity, and UCP family in mice. Diabetes 50:385–391
5HT2C
Nonogaki K, Strack AM, Dallman MF, Tecott LH 1998 Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat Med 4:1152–1156[CrossRef][Medline]
Lucas JJ, Yamamoto A, Scearce-Levie K, Saudou F, Hen R 1998 Absence of fenfluramine-induced anorexia and reduced c-fos induction in the hypothalamus and central amygdaloid complex of serotonin 1B receptor knock-out mice. J Neurosci 18:5537–5544
5HT1B
Nonogaki K, Strack AM, Dallman MF, Tecott LH 1998 Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat Med 4:1152–1156[CrossRef][Medline]
Lucas JJ, Yamamoto A, Scearce-Levie K, Saudou F, Hen R 1998 Absence of fenfluramine-induced anorexia and reduced c-fos induction in the hypothalamus and central amygdaloid complex of serotonin 1B receptor knock-out mice. J Neurosci 18:5537–5544
Insulin Receptor
Bruning JC, Gautum D, Burks DJ, Gillette J, Schubert M, Orban PC, Klein R, Crone W, Muller-Weiland D, Kahn CR 2000 Role of insulin receptor in control of body weight and reproduction. Science 289:2122–2125
Leptin Receptor
Chen H, Charlat O, Tartaglia LA, Woolf EA, Weng X, Ellis SJ, Lakey ND, Culpepper J, Moore KJ, Breitbart RE, Duyk GM, Tepper RI, Morgenstern JP 1996 Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell 84:491–495[CrossRef][Medline]
Lee G-H, Proenca R, Montez JM, Caroll KM, Darvishzadeh JG, Lee JI, Freidman JM 1996 Abnormal splicing of the leptin receptor in diabetic mice. Nature 379:632–635[CrossRef][Medline]
Phillips MS, Liu Q, Hammond HA, Dugan V, Hey PJ, Casker CT, Hess JF 1996 Leptin receptor missense mutation in the fatty Zucker rat. Nat Genet 13:18–19[CrossRef][Medline]
Iida M, Muraakami T, Ishida K, Mizuno A, Kuwajima M, Shima K 1996 Phenotype-linked amino acid alteration in leptin receptor cDNA from Zucker fatty (fa/fa) rat. Biochem Biophys Res Commun 222:19–26[CrossRef][Medline]
Takaya K, Ogawa Y, Hiraoka J, Hosoda K, Yamori Y, Nakao K, Koletsky RJ 1996 Nonsense mutation of leptin receptor in the obese spontaneously hypertensive Koletsky rat. Nat Genet 14:130–131[CrossRef][Medline]
Kowalski TJ, Liu SM, Leibel RL, Chua Jr SC 2001 Transgenic complementation of leptin-receptor deficiency. I. Rescue of the obesity/diabetes phenotype of LEPR-null mice expressing a LEPR-B transgene. Diabetes 50:425–435
Chua Jr SC, Liu SM, Li Q, Sun A, DeNino WF, Heymsfield SB, Guo XE 2004 Transgenic complementation of leptin receptor deficiency. II. Increased leptin receptor transgene dose effects on obesity/diabetes and fertility/lactation in lepr-db/db mice. Am J Physiol 286:E384–E392
MC3 and MC4
Chen AS, Marsh DJ, Trumbauer ME, Frazier EG, Guan X-M, Yu H, Rosenblum CI, Vongs A, Feng Y, Cao L, Metzger JM, Strack AM, Camacho RE, Mellin TN, Nunes CN, Min W, Fisher J, Gopal-Truter S, MacIntyre DE, Chen HY, Van der Ploeg LHT 2000 Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat Genet 26:97–102[CrossRef][Medline]
Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, Berkemeier L, Gu W, Kesterson RA, Boston BA, Cone RD, Smith FJ, Campfield LA, Burn P, Lee F 1997 Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88:131–14[CrossRef][Medline]
Melanin Concentrating Hormone Receptor 1
Marsh DJ, Weingarth DT, Novi DE, Chen HY, Trumbauer ME, Chen AS, Guan XM, Jiang MM, Feng Y, Camacho RE, Shen Z, Frazier EG, Yu H, Metzger JM, Kuca SJ, Shearman LP, Gopal-Truter S, MacNeil DJ, Strack AM, MacIntyre DE, Van der Ploeg LH, Qian S 2002 Melanin concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Proc Natl Acad Sci USA 99:3240–3245
Muscarinic M3R
Yamada M, Miyakawa T, Duttaroy A, Yamanaka A, Moriguchi T, Makita R, Ogawa M, Chou CJ, Xia B, Crawley JN, Felder CC, Deng CX, Wess J 2001 Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean. Nature 410:207–212[CrossRef][Medline]
NPY Receptors
Sainsbury A, Baldock PA, Schwarzer C, Ueno N, Enriquez RF, Couzens M, Inui A, Herzog H, Gardiner EM 2003 Synergistic effects of Y2 and Y4 receptors on adiposity and bone mass revealed in double knockout mice. Mol Cell Biol 23:5225–5233
Syndecans
Bellin R, Capila I, Lincecum J, Park PW, Reizes O, Bernfield MR 2002 Unlocking the secrets of syndecans: transgenic organisms as a potential key. Glycoconj J 19:295–304[CrossRef][Medline]
Syndecan 1
Reizes O, Lincecum J, Wang Z, Goldberger O, Huang L, Kaksonen M, Ahima R, Hinkes MT, Barsh GS, Rauvala H, Bernfield M 2001 Transgenic expression of syndecan-1 uncovers a physiological control of feeding behavior by syndecan-3. Cell 106:105–116[CrossRef][Medline]
Syndecan 3
Reizes O, Lincecum J, Wang Z, Goldberger O, Huang L, Kaksonen M, Ahima R, Hinkes MT, Barsh GS, Rauvala H, Bernfield M 2001 Transgenic expression of syndecan-1 uncovers a physiological control of feeding behavior by syndecan-3. Cell 106:105–116[CrossRef][Medline]
Bellin R, Capila I, Lincecum J, Park PW, Reizes O, Bernfield MR 2002 Unlocking the secrets of syndecans: transgenic organisms as a potential key. Glycoconj J 19:295–304[CrossRef][Medline]
TNF2P75
Schreyer SA, Chua Jr SC, LeBoeuf RC 1998 Obesity and diabetes in TNF- receptor-deficient mice. J Clin Invest 102:402–411[Medline]
II. HORMONES/PEPTIDES
Agouti
Wolff GC 1965 Body composition and coat color correlation in different phenotypes of "viable yellow" mice. Science 147:1145–1147
Bultman SJ, Michaud EJ, Woychik RP 1992 Molecular characterization of the mouse agouti locus. Cell 71:1195–1204[CrossRef][Medline]
Perry W, Hustad C, Swing D, Jenkins N, Copeland N 1995 A transgenic mouse assay for agouti protein activity. Genetics 140:267–274[Abstract]
Klebig ML, Wilkinson JE, Geisler, JG, Woychik RP 1995 Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur. Proc Natl Acad Sci USA 92:4728–4732
Wilson BD, Ollman MM, Kany L, Stoffer M, Bell GI, Barsch GS 1995 Structure and function of ASP, the human homolog of the mouse agouti gene. Hum Mol Genet 4:223–230
Ollman MM, Wilson BD, Yang Y-K, Kerns JA, Chen Y, Gantz I, Barsh GS 1997 Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278:135–138
Mynatt RL, Stephens JM 2003 Regulation of PPAR and obesity by agouti/melanocortin signaling in adipocytes. Ann NY Acad Sci 994:141–146[Medline]
AgRP
Ollman MM, Wilson BD, Yang Y-K, Kerns JA, Chen Y, Gantz I, Barsh GS 1997 Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278:135–138
Graham M, Shutter JR, Sarmiento U, Sarosi I, Stark KL 1997 Overexpression of Agrt leads to obesity in transgenic mice. Nat Genet 17:273–274[CrossRef][Medline]
Amylin
Devine E, Young AA 1998 Weight gain in male and female mice with amylin gene knockout. Diabetes 47:A317 (Abstract)
CRH
Stenzel-Poore MP, Cameron VA, Vaughan J, Sawchenko PE, Vale W 1992 Development of Cushing’s syndrome in corticotropin-releasing factor transgenic mice. Endocrinology 130:3378–3386[Abstract]
CRH Binding Protein
Karolyi IJ, Burrows HL, Ramesh TM, Nakajima M, Lesh JS, Seong E, Camper SA, Seasholtz AF 1999 Altered anxiety and weight gain in corticotropin-releasing hormone-binding protein-deficient mice. Proc Natl Acad Sci USA 96:11595–11600
Lovejoy DA, Aubry JM, Turnbull A, Sutton S, Potter E, Yehling J, Rivier C, Vale WW 1998 Ectopic expression of the CRF-binding protein: minor impact on HPA axis regulation but induction of sexually dimorphic weight gain. J Neuroendocrinol 10:483–491[CrossRef][Medline]
Growth Hormone
Searle TW, Murray JD, Baker PJ 1992 Effect of increased production of GH on body composition in mice: transgenic vs. control. J Endocrinol 132:285–291
Cai A, Hyde JF 1999 The human GH-releasing hormone transgenic mouse as a model of modest obesity: differential changes in leptin receptor (OBR) gene expression in the anterior pituitary and hypothalamus after fasting and OBR localization in somatotrophs. Endocrinology 140:3609–3614
Donahue LR, Beamer WG 1993 GH deficiency in "little" mice results in aberrant body composition, reduced insulin-like growth factor-I and insulin-like grown factor-binding protein-3 (IGFBP-3), but does not affect IGFBP-2, -1 or -4. J Endocrinology 136:91–104
Oberbauer AM, Runstadler JA, Murray JD, Havel PJ 2001 Obesity and elevated plasma leptin concentration in oMT1A-o GH transgenic mice. Obes Res 9:51–58[Medline]
GHRH
Cai A, Hyde JF 1999 The human GH-releasing hormone transgenic mouse as a model of modest obesity: differential changes in leptin receptor (OBR) gene expression in the anterior pituitary and hypothalamus after fasting and OBR localization in somatotrophs. Endocrinology 140:3609–3614
Insulin-Like Growth Factor 1 Binding Protein
Rajkumar K, Modric T, Murphy LJ 1999 Impaired adipogenesis in insulin-like growth factor binding protein-1 transgenic mice. J Endocrinol 162:457–465[Abstract]
IL-1 Receptor Antagonist
Hirsch E, Irikura VM, Paul SM, Hirsh D 1996 Functions of interleukin 1 receptor antagonist in gene knockout and overproducing mice. Proc Natl Acad Sci USA 93:11008–11013
IL-6
Wallenius V, Wallenius K, Ahren B, Rudling M, Carlsten H, Dickson SL, Ohlsson C, Jansson JO 2002 Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 8:75–79[CrossRef][Medline]
Leptin
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM 1994 Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432[CrossRef][Medline]
Masuzaki H, Ogawa Y, Aizawa-Abe M, Hosoda K, Suga J, Ebihara K, Satoh N, Iwai H, Inoue G, Nishimura H, Yoshimasa Y, Nakao K 1999 Glucose metabolism and insulin sensitivity in transgenic mice overexpressing leptin with lethal yellow agouti mutation: usefulness of leptin for the treatment of obesity-associated diabetes. Diabetes 48:1615–1622[Abstract]
Shimomura I, Hammer RE, Ikemoto S, Brown MS, Goldstein JL 1999 Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 401:73–76[CrossRef][Medline]
Ebihara K, Ogawa Y, Masuzaki H, Shintani M, Miyanaga F, Aizawa-Abe M, Hayashi T, Hosoda K, Inoue G, Yoshimasa Y, Gavrilova O, Reitman ML, Nakao K 2001 Transgenic overexpression of leptin rescues insulin resistance and diabetes in a mouse model of lipoatrophic diabetes. Diabetes 50:1440–1448
Ogus S, Ke Y, Qiu J, Wang B, Chehab FF 2003 Hy-perleptinemia precipitates diet-induced obesity in transgenic mice overexpressing leptin. Endocrinology 144:2865–2869
LH
Kero JT, Savontaus E, Mikola M, Pesonen U, Koulu M, Keri RA, Nilson JH, Poutanen M, Huhtaniemi IT 2003 Obesity in transgenic female mice with constitutively elevated LH secretion. Am J Physiol 285:E812–E818
Mahogany (mg)
Miller KA, Gunn TM, Carrasquillo MM, Lamoreaux ML, Galbraith DB, Barsh GS 1997 Genetic studies of the mouse mutations mahogany and mahoganoid. Genetics 146:1407–1415[Abstract]
Gunn TM, Miller KA, He L, Hyman RW, Davis RW, Azarani A, Schlossman SF, Duke-Cohan JS, Barsh GS 1999 The mouse mahogany locus encodes a transmembrane form of human attractin. Nature 398:152–156[CrossRef][Medline]
Mahogonoid (Md)
Miller KA, Gunn TM, Carrasquillo MM, Lamoreaux ML, Galbraith DB, Barsh GS 1997 Genetic studies of the mouse mutations mahogany and mahoganoid. Genetics 146:1407–1415[Abstract]
Gunn TM, Miller KA, He L, Hyman RW, Davis RW, Azarani A, Schlossman SF, Duke-Cohan JS, Barsh GS 1999 The mouse mahogany locus encodes a transmembrane form of human attractin. Nature 398:152–156[CrossRef][Medline]
Melanin Concentrating Hormone (MCH)
Shimada M, Tritos NA, Lowell BB, Flier JS, Maratos-Flier E 1998 Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature 396:670–674[CrossRef][Medline]
Ludwig DS, Tritos NA, Mastaitis JW, Kulkarni R, Kokkotou E, Elmquist J, Lowell B, Flier JS, Maratos-Flier E 2001 Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. J Clin Invest 107:379–386[Medline]
NPY
Bannon AW, Seda J, Carmouche M, Francis JM, Norman MH, Karbon B, McCaleb ML 2000 Behavioral characterization of neuropeptide Y knockout mice. Brain Res 868:79–87[CrossRef][Medline]
Erickson JC, Hollopeter G, Palmiter JD 1996 Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y. Science 274:1704–1707
Herzog H 2003 Neuropeptide Y and energy homeostasis: insights from Y receptor knockout models. Eur J Pharmacol 480: 21–29[CrossRef][Medline]
Orexin (Hypocretin)
Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y, Fitch TE, Nakazato M, Hammer RE, Saper CB, Yanagisawa M 1999 Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98:437–451[CrossRef][Medline]
Pancreatic Polypeptide
Ueno N, Inui A, Iwamato M, Kaga T, Asakawa A, Okita M, Fujimiya M, Nakajami Y, Ohmoto Y, Ohnaka M, Nakaya Y, Miyazaki JI, Kasuga M 1999 Decreased food intake and body weight in pancreatic polypeptide-overexpressing mice. Gastroenterology 117:1427–1432[CrossRef][Medline]
Plasminogen Activator Inhibitor-1
Lijnen HR, Maquoi E, Morange P, Voros G, Van Hoef B, Kopp F, Collen D, Juhan-Vague I, Alessi MC 2003 Nutritionally induced obesity is attenuated in transgenic mice overexpressing plasminogen activator inhibitor-1. Arterioscler Thromb Vasc Biol 23:78–84
POMC
Yaswen L, Diehl N, Brennan MB, Hochgeschwender U 1999 Obesity in the mouse model of POMC deficiency responds to peripheral melanocortin. Nat Med 5:1066–1117[CrossRef][Medline]
Mizuno TM, Kelley KA, Pasinetti GM, Roberts JL, Mobbs CV 2003 Transgenic neuronal expression of POMC attenuates hyperphagic response to fasting and reverses metabolic impairments in leptin-deficient obese mice. Diabetes 52:2675–2683
Renin
Uehara S, Tsuchida M, Kanno T, Sasaki M, Nishikibe M, Fukamizu A 2003 Late-onset obesity in mice transgenic for the human renin gene. Int J Mol Med 11:723–727[Medline]
TGF1ß
Clouthier DE, Comerford SA, Hammer RE 1997 Hepatic fibrosis, glomerulosclerosis and a lipodystrophy-like syndrome in PEPCK-TGF-ß1 transgenic mice. J Clin Invest 100:2697–2713[Medline]
TNF
Hotamisligil GS, Shargill NS, Spiegelman BM 1993 Adipose expression of tumor necrosis factor-: direct role in obesity-linked insulin resistance. Science 259:87–91
Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS 1997 Protection from obesity-induced insulin resistance in mice lacking TNF- function. Nature 389:610–614[CrossRef][Medline]
III. ENZYMES/METABOLIC
Acetyl CoA Carboxylase 2
Abu-Elheiga L, Matzuk MM, Abo-Hashema KAH, Wakil SJ 2001 Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-co-A carboxylase 2. Science 291:2613–2616
ASP
Murray SE, Coste SC, Lindberg I, Stenzel-Poore MP 2000 Genetic mutants with dysregulation of corticotropin pathways. In: Castro M, ed. Transgenic models of endocrinology. New York: Kluger
AcylCoA-Diacylglycerolacyl transferase (DGAT)
Smith SJ, Cases S, Jensen DR, Chen HC, Sande E, Tow B, Sanan DA, Raber J, Eckel RH, Farese Jr RV 2000 Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nat Genet 25:87–90[CrossRef][Medline]
Chen HC, Jensen DR, Myers HM, Eckel RH, Farese Jr RV 2003 Obesity resistance and enhanced glucose metabolism in mice transplanted with white adipose tissue lacking acyl CoA:diacylglycerol acyltransferase 1. J Clin Invest 111: 1715–1722[CrossRef][Medline]
Aromatase
Jones MEE, Thorburn AW, Britt KL, Hewitt KN, Wreford NG, Proietto J, Oz OK, Leury BJ, Robertson KM, Yao S, Simpson ER 2000 Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity. Proc Natl Acad Sci USA 97:12735–12740
7B2
Westphal CH, Muller L, Zhou A, Zhu X, Bonner-Weir S, Schambelan M, Steiner DF, Lindberg I, Leder P 1999 The neuroendocrine protein 7B2 is required for peptide hormone processing in vivo and provides a novel mechanism for pituitary Cushing’s disease. Cell 96:689–700[CrossRef][Medline]
Glucokinase
Otaegui PJ, Ferre T, Riu E, Bosch F 2003 Prevention of obesity and insulin resistance by glucokinase expression in skeletal muscle of transgenic mice. FASEB J 17:2097–2099
Glutamine:Fructose-6-Phosphate Amino Transferase
Veerababu G, Tang J, Hoffman RT, Daniels MC, Hebert LF Jr, Crook ED, Cooksey RC, McClain DA 2000 Overexpression of gluatamine: fructose-6-phosphate amidotransferase in the liver of transgenic mice results in enhanced glycogen storage, hyperlipidemia, obesity, and impaired glucose tolerance. Diabetes 49:2070–2078
Glut4
Stenbit AE, Tsao TS, Li J, Burcelin R, Geenen DL, Factor SM, Houseknecht K, Katz EB, Charron MJ 1997 GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes. Nat Med 3:1080–1081[CrossRef][Medline]
Shepherd PR, Gnudi L, Tozzo E, Yang H, Leach F, Kahn BB 1993 Adipose cell hyperplasia and enhanced glucose disposal in transgenic mice overexpressing GLUT4 selectively in adipose tissue. J Biol Chem 268:22243–22246
G3PDH
Kozak LP, Kozak UC, Clarke GT 1991 Abnormal brown and white fat development in transgenic mice overexpressing glycerol 3-phosphate dehydrogenase. Genes 5:2256–2264
Eto K, Tsubamoto Y, Terauchi Y, Sugiyama T, Kishimoto T, Takahashi N, Yamauchi N, Kubota N, Murayama S, Aizawa T, Akanuma Y, Kasai H, Yazaki Y, Kadowaki T 1999 Role of NADH shuttle system in glucose-induced activation of mitochondrial metabolism and insulin secretion. Science 283:981–985
HSL
Osuga J, Ishibashi S, Oka T, Yaguy H, Tozawa R, Fujimoto A, Shionoiri F, Yahagi N, Kraemer FB, Tsutsumi O, Yamada N 2000 Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity. Proc Natl Acad Sci USA 97:787–792
11-ß-Hydroxysteroid Dehydrogenase
Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR, Flier JS 2001 Atransgenic model of visceral obesity and the metabolic syndrome. Science 294:2166–2170
Masuzaki H, Yamamoto H, Kenyon CJ, Elmquist JK, Morton NM, Paterson JM, Shinyama H, Sharp MG, Fleming S, Mullins JJ, Seckl JR, Flier JS 2003 Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice. J Clin Invest 112: 83–90[CrossRef][Medline]
LPL
Koike T, Liang J, Wang X, Ichikawa T, Shiomi M, Liu G, Sun H, Kitajima S, Morimoto M, Watanabe T 2004 Overexpression of lipoprotein lipase in transgenic watanabe heritable hyperlipidemic rabbits improves hyperlipidemia and obesity. J Biol Chem 279:7521–7529
Perilipin
Martinez-Botas J, Anderson JB, Tessier D, Lapillonne A, Change BH-J, Quast MJ, Gorenstein D, Chen K-H, Chan L 2000 Absence of perilipin results in leanness and reverses obesity in Leprdb/db mice. Nat Genet 26:474–479[CrossRef][Medline]
Tansey JT, Sztalryd C, Gruia-Gray J, Roush DL, Zee JV, Gavrilova O, Reitman ML, Deng C-X, Li C, Kimmel AR, Londos C 2001 Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production, and resistance to diet-induce obesity. Proc Natl Acad Sci 98:6494–6499
Stearoyl CoA Desaturase
Ntambi JM, Miyazaki M, Stoehr JP, Lan H, Kendziorski CM, Yandell BS, Song Y, Cohen P, Friedman JM, Attie AD 2002 Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity. Proc Natl Acad Sci USA 99: 11482–11486
Cohen P, Miyazaki M, Socci ND, Hagge-Greenberg A, Liedtke W, Soukas AA, Sharma R, Hudgkins LC, Ntambi JM, Firedman JM 2002 Role of stearoyl-CoA desaturase-1 on leptin-mediated weight loss. Science 297: 240–243
Tyrosine Hydroxylase
Zhou QY, Quaife CJ, Palmiter RD 1995 Targeted disruption of the tyrosine hydroxylase gene reveals that catecholamines are required for mouse fetal development. Nature 374:640–643[CrossRef][Medline]
Zhou QV, Palmiter RD 1995 Dopamine deficient mice are severely hypoactive, adipsic and aphagic. Cell 83:1197–1209[CrossRef][Medline]
UCP1
Kopecky J, Hodny Z, Rossmeisl M, Syrovy I, Kozak LP 1996 Reduction of dietary obesity in aP2-Ucp transgenic mice: physiology and adipose tissue distribution. Am J Physiol 270:E768–E775[Medline]
Li B, Nolte LA, Ju JS, Han DH, Coleman T, Holloszy JO, Semenkovich CF 2000 Skeletal muscle respiratory uncoupling prevents diet-induced obesity and insulin resistance in mice. Nat Med 6:1115–1120[CrossRef][Medline]
Enerback S, Jacobsson A, Simpson EM, Guerra C, Yamashita H, Harper M-E, Kozak LE 1997 Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 387:90–94[CrossRef][Medline]
UCP2 and UCP3
Gong D-W, Monemdjou S, Gavrilova O, Leon LR, Marcus-Samuels B, Chou CJ, Everett C, Kozak LP, Li C, Deng C, Harper M-E, Reitman ML 2000 Lack of obesity and normal response to fasting and thyroid hormone in mice lacking uncoupling protein-3. J Biol Chem 275:16251–16257
Clapham JC, Arch JR, Chapman H, Haynes A, Lister C, Moore GB, Piercy V, Carter SA, Lehner I, Smith SA, Beeley LJ, Godden RJ, Herrity N, Skehel M, Changani KK, Hockings PD, Reid DG, Squires SM, Hatcher J, Trail B, Latcham J, Rastan S, Harper AJ, Cadenas S, Buckingham JA, Brand MD, Abuin A 2000 Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean. Nature 406:415–418[CrossRef][Medline]
Horvath TL, Diano S, Miyamoto S, Barry S, Gatti S, Alberati D, Livak F, Lombardi A, Moreno M, Goglia F, Mor G, Hamilton J, Kachinskas D, Horwitz B, Warden CH 2003 Uncoupling proteins-2 and 3 influence obesity and inflammation in transgenic mice. Int J Obes Relat Metab Disord 27:433–442[CrossRef][Medline]
Son C, Hosoda K, Ishihara K, Bevilacqua L, Masuzaki H, Fushiki T, Harper ME, Nakao K 2004 Reduction of diet-induced obesity in transgenic mice overexpressing uncoupling protein 3 in skeletal muscle. Diabetologia 47:47–54[CrossRef][Medline]
UCP1-Diphtheria Toxin A Chain Transgene
Lowell BB, S-Susulic V, Hamann A, Lawitts JA, Himms-Hagen J, Boyers BB, Kozak LP, Flier JS 1993 Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature 366:740–742[CrossRef][Medline]
IV. SIGNALING PROTEINS/MOLECULES
Gs
Yu S, Gavrilova O, Chen H, Lee R, Liu J, Pacak K, Parlow AF, Quon MJ, Reitman ML, Weinstein LS 2000 Paternal vs. maternal transmission of a stimulatory G-protein subunit knockout produces opposite effects on energy metabolism. J Clin Invest 105:615–623[Medline]
JNK
Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS 2002 A central role for JNK in obesity and insulin resistance. Nature 420:333–336[CrossRef][Medline]
Metallothionein I and II
Beattie JH, Wood AM, Newman AM, Bremner I, Choo KHA, Michalska AE, Duncan JS, Trayhurn P 1998 Obesity and hyperleptinemia in metallothionein (-I and -II). Proc Natl Acad Sci USA 95:358–363
eNOS
Nisoli E, Clementi E, Paolucci C, Cozzi V, Tonello C, Sciorati C, Bracale R, Valerio A, Francolini M, Moncada S, Carruba MO 2003 Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science 299:896–899
PKARIIß
McKnight SL 1998 WAT-free mice: diabetes without obesity. Genes Dev 12: 3145–3148
McKnight SL, Cummings DE, Amieux PS, Sikorski MA, Brandon EP, Planas JV, Motamed K, Idzerda RL 1998 Cyclic AMP, PKA and the physiological regulation of adiposity. Rec Prog Horm Res 53: 139–159[Medline]
PTP1B
Elchebly M, Payette P, Michaliszyn E, CromLish W, Collins S, Loy AL, Normandin D, Cheng A, Himms-Hagen J, Chan C-C, Ramachandran C, Gresser MJ, Tremblay ML, Kennedy BP 1999 Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science 283:1544–1548
PKC-
Serra C, federici M, Buongiorno A, Senni MI, Morelli S, Segratella E, Pascuccio M, Tiveron C, Mattei E, Tantangelo L, Lauro R, Molinaro M, Giaccari A, Bouche M 2003 Transgenic mice with dominant negative PKC- in skeletal muscle: a new model of insulin resistance and obesity. J Cell Physiol >196>: 89–97[Medline]
SPARC
Bradshaw AD, Graves DC, Motamed K, Sage EH 2003 SPARC-null mice exhibit increased adiposity without significant differences in overall body weight. Proc Natl Acad Sci USA 100:6045–6050
V. TRANSCRIPTION FACTORS/NUCLEAR PROTEINS
aP2
Hotamisligil GS, Johnson RS, Distel RJ, Ellis R, Papaioannou VE, Siegelman BM 1996 Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science 274:1377–1379
AZIP/F
Reitman ML, Gavrilova O 2000 A-ZIP/F-1 mice lacking white fat: a model for understanding lipoatrophic diabetes. Int J Obes Rel Metab Disord 24(Suppl 4):S11–S14
C/EBPs
Wang ND, Finegold MJ, Bradley A, Ou CN, Abdelsayed SV, Wilde MD, Taylor LR, Wilson DR, Darlington GJ 1995 Impaired energy homeostasis in C/EBP knockout mice. Science 269:1108–1112
Tanaka T, Yoshida N, Kishimoto T, Akira S 1997 Defective adipocyte differentiation in mice lacking the C/EBPß and/or C/EBP
gene. EMBO J 16:7432–7443[CrossRef][Medline]
FOXA-2
Wolfrum C, Shih DQ, Kuwajima S, Norris AW, Kahn CR, Stoffel M 2003 Role of Foxa-2 in adipocyte metabolism and differentiation. J Clin Invest 112:345–356[CrossRef][Medline]
FOXC-2
Cederberg A, Gronning LM, Ahren B, Tasken K, Carlsson P, Enerback S 2001 FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance. Cell 106:563–573[CrossRef][Medline]
Lipin
Peterfy M, Phan J, Xu P, Reue K 2001 Lipodystrophy in the f/d mouse results from mutation of a new gene encoding a nuclear protein, lipin. Nat Genet 27:121–124[CrossRef][Medline]
c-Myc
Riu E, Ferre T, Hidalgo A, Mas A, Franckhauser S, Otaegui P, Bosch F 2003 Overexpression of c-myc in the liver prevents obesity and insulin resistance. FASEB J 17:1715–1717
Nhlh2
Good DJ, Porter FD, Mahon KA, Parlow AF, Westphal H, Kirsch JR 1997 Hypogonadism and obesity in mice with a targeted deletion of the Nhih2 gene. Nat Genet 15:397–401[CrossRef][Medline]
PPAR
Costet P, Legendre C, More J, Edgar A, Galtier P, Pineau T 1998 Peroxisome proliferator-activated receptor -isoform deficiency leads to progressive dyslipidemia with sexually dimorphic obesity and steatosis. J Biol Chem 273:29577–29585
PPAR
Wang YX, Lee CH, Tiep S, Yu RT, Ham J, Kang H, Evans RM 2003 Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity. Cell 113:159–170[CrossRef][Medline]
PPAR Coactivator 1ß/ERR Ligand 1
Kamei Y, Ohizumi H, Fujitani Y, Nemoto T, Tanaka T, Takahashi N, Kawada T, Miyoshi M 2003 PPAR coactivator 1ß/ERR ligand 1 is an ERR protein ligand, whose expression induces a high-energy expenditure and antagonizes obesity. Proc Natl Acad Sci USA 100:12378–12383
RXR
Imai T, Jiang M, Chambon P, Metzger D 2001 Impaired adipogenesis and lipolysis in the mouse upon selective ablation of the retinoid X receptor alpha mediated by a tamoxifen-inducible chimeric Cre recombinase (Cre-ERT2) in adipocytes. Proc Natl Acad Sci USA 98:224–228
SRC-1
Picard F, Gehin M, Annicotte J, Rocchi S, Champy MF, O’Malley BW, Chambon P, Auwerx J 2002 SRC-1 and TIF2 control energy balance between white and brown adipose tissues. Cell 111:931–941[CrossRef][Medline]
SREBP-1C and -1A
Shimomura I, Hammer RE, Richardson JA, Ikemoto S, Bashmakov Y, Goldstein JL, Brown MS 1998 Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes Dev 12:3182–3194
Shimano H, Horton JD, Hammer RE, Shimomura I, Brown MS, Goldstein JL 1996 Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a. J Clin Invest 98:1575–1584[Medline]
STAT5
Udy GB, Towers RP, Snell RG, Wilkins RJ, Park SH, Ram PA, Waxman DJ, Davey HW 1997 Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression. Proc Natl Acad Sci USA 94:7239–7244
TIF-2
Picard F, Gehin M, Annicotte J, Rocchi S, Champy MF, O’Malley BW, Chambon P, Auwerx J 2002 SRC-1 and TIF2 control energy balance between white and brown adipose tissues. Cell 111:931–941[CrossRef][Medline]
VgF
Hahm S, Mizuno TM, WU TJ, Wisor JP, Priest CA, Kozak CA, Boozer CN, Peng B, McEvoy RC, Good P, Kelley KA, Takahashi JS, Pintar JE, Roberts JL, Mobbs CV, Salton SR 1999 Targeted deletion of the VgF gene indicates that the encoded secretory peptide precursor plays a novel role in the regulation of energy balance. Neuron 23:537–548[CrossRef][Medline]
VI. STRUCTURAL
Hmgic
Anand A, Chada K 2000 In vivo modulation of Hmgic reduces obesity. Nat Genet 24:377–80[CrossRef][Medline]
ICAM-1
Dong ZM, Gutierrez-Ramos JC, Coxon A, Mayadas TN, Wagner DD 1997 A new class of obesity genes encodes leukocyte adhesion receptors. Proc Natl Acad Sci USA 4:7526–7530
Footnotes
1 We thank David York for providing this segment of the Genetically Modified Animals in Endocrinology Bibliography Project. Dr. York is with the Pennington Biomedical Research Center in Baton Rouge, Louisiana. 
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