Mouse Models for Studying Metabolism

We have extensive experience and a strong track record in the design of mouse models as genetic tools for research in glycogen and lipid metabolism, hormonal coordination of metabolism, nutrition, etc. allowing the study of medical metabolic conditions such as obesity, lipodystrophy, polyglucosan disorders, type 1 diabetes, type 2 diabetes, bone-mineral metabolic disorders or muscle glycogen disorders, to mention a few.

genOway has been providing mouse and rat models to scientists from academic institutions (Imperial College London, Frankfurt University, Kansas University, Oslo University, Tufts University, etc.), pharmaceutical industries and biotechnology companies (BMS, Mellitech, Nestlé, Pfizer, Servier Laboratories, etc.) for studying:

  • Metabolic functions under both normal and pathologic conditions (insulin secretion, plasma ultrafiltration, renal hormone excretion, kidney and intestine structure, etc.).
  • Drug targets (humanization of receptor and signaling molecules, monitoring of pathway activations, etc.).
  • New tools for hormone monitoring, cell response assessment, etc.

Do not hesitate to contact our scientific experts to discuss any project you have in mind. Receive a free consultation enabling you to evaluate the value our experience, expertise and technologies in the design of genetically modified models will bring to your project.


Below you will find a selection of references for models we have created for our clients:

Medical Metabolic Conditions

Type 1 Diabetes:
Lemaire K, Ravier MA, Schraenen A, Creemers JW, Van de Plas R, Granvik M, Van Lommel L, Waelkens E, Chimienti F, Rutter GA, Gilon P, in't Veld PA, Schuit FC.
Insulin crystallization depends on zinc transporter ZnT8 expression, but is not required for normal glucose homeostasis in mice.
Proc Natl Acad Sci U S A. 2009

Type 2 Diabetes:
Mehta ZB, Fine N, Pullen TJ, Cane MC, Hu M, Chabosseau P, Meur G, Velayos-Baeza A, Monaco AP, Marselli L, Marchetti P, Rutter GA.
Changes in the expression of the type 2 diabetes-associated gene VPS13C in the β-cell are associated with glucose intolerance in humans and mice.
Am J Physiol Endocrinol Metab. 2016

Li LC, Wang Y, Carr R, Haddad CS, Li Z, Qian L, Oberholzer J, Maker AV, Wang Q, Prabhakar BS
IG20/MADD Plays a Critical Role in Glucose-Induced Insulin Secretion.
Diabetes. 2014

Hardy AB, Wijesekara N, Genkin I, Prentice KJ, Bhattacharjee A, Kong D, Chimienti F, Wheeler MB.
Effects of high-fat diet feeding on Znt8-null mice: differences between β-cell and global knockout of Znt8.
Am J Physiol Endocrinol Metab. 2012

da Silva Xavier G, Mondragon A, Sun G, Chen L, McGinty JA, French PM, Rutter GA.
Abnormal glucose tolerance and insulin secretion in pancreas-specific Tcf7l2-null mice.
Diabetologia. 2012

SHORT syndrome:
Winnay JN, Solheim MH, Dirice E, Sakaguchi M, Noh HL, Kang HJ, Takahashi H, Chudasama KK, Kim JK, Molven A, Kahn CR, Njølstad PR.
PI3-kinase mutation linked to insulin and growth factor resistance in vivo.
J Clin Invest. 2016

Glucose intolerance:
Sun G, Tarasov AI, McGinty J, McDonald A, da Silva Xavier G, Gorman T, Marley A, French PM, Parker H, Gribble F, Reimann F, Prendiville O, Carzaniga R, Viollet B, Leclerc I, Rutter GA.
Ablation of AMP-activated protein kinase alpha1 and alpha2 from mouse pancreatic beta cells and RIP2.Cre neurons suppresses insulin release in vivo.
Diabetologia. 2010

Glycogen storage disease type III:
Pagliarani S, Lucchiari S, Ulzi G, Violano R, Ripolone M, Bordoni A, Nizzardo M, Gatti S, Corti S, Moggio M, Bresolin N, Comi GP
Glycogen storage disease type III: A novel Agl knockout mouse model.
Biochim Biophys Acta. 2014

Obesity:
Yavari A, Stocker CJ, Ghaffari S, Wargent ET, Steeples V, Czibik G, Pinter K, Bellahcene M, Woods A, Martínez de Morentin, Cansell C, Lam BY, Chuster A, Petkevicius K, Nguyen-Tu MS, Martinez-Sanchez A, Pullen TJ, Oliver PL, Stockenhuber A, Nguyen C, Lazdam M, O'Dowd JF, Harikumar P, Tóth M, Beall C, Kyriakou T, Parnis J, Sarma D, Katritsis G, Wortmann DD, Harper AR, Brown LA, Willows R, Gandra S, Poncio V, de Oliveira Figueiredo MJ, Qi NR, Peirson SN, McCrimmon RJ, Gereben B, Tretter L, Fekete C, Redwood C, Yeo GS, Heisler LK, Rutter GA, Smith MA, Withers DJ, Carling D, Sternick EB, Arch JR, Cawthorne MA, Watkins H, Ashrafian H.
Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function.
Cell Metab. 2016

Lengacher S, Nehiri-Sitayeb T, Steiner N, Carneiro L, Favrod C, Preitner F, Thorens B, Stehle JC, Dix L, Pralong F, Magistretti PJ, Pellerin L.
Resistance to diet-induced obesity and associated metabolic perturbations in haploinsufficient monocarboxylate transporter 1 mice.
PLoS One. 2013

Solberg A, Robertson AB, Aronsen JM, Rognmo O, Sjaastad I, Wisløff U, Klungland A.
Deletion of mouse Alkbh7 leads to obesity.
J Mol Cell Biol. 2013

Della-Zuana O, Audinot V, Levenez V, Ktorza A, Presse F, Nahon JL, Boutin JA.
Peripheral injections of melanin-concentrating hormone receptor 1 antagonist S38151 decrease food intake and body weight in rodent obesity models.
Front Endocrinol. 2012

Energy homeostasis:
Chen J, Kaiyala KJ, Lam J, Agrawal N, Nguyen L, Ogimoto K, Spencer D, Morton GJ, Schwartz MW, Dichek HL.
In vivo structure-function studies of human hepatic lipase: the catalytic function rescues the lean phenotype of HL-deficient (hl-/-) mice.
Physiol Rep. 2015

Thermogenesis:
Dodd GT, Worth AA, Nunn N, Korpal AK, Bechtold DA, Allison MB, Myers MG Jr, Statnick MA, Luckman SM
The Thermogenic Effect of Leptin Is Dependent on a Distinct Population of Prolactin-Releasing Peptide Neurons in the Dorsomedial Hypothalamus.
Cell Metab. 2014

Chronic hyperammonemia:
Qvartskhava N, Lang PA, Görg B, Pozdeev VI, Ortiz MP, Lang KS, Bidmon HJ, Lang E, Leibrock CB, Herebian D, Bode JG, Lang F, Häussinger D.
Hyperammonemia in gene-targeted mice lacking functional hepatic glutamine synthetase.
Proc Natl Acad Sci U S A. 2015

Fatty Liver Disease:
McManaman JL, Bales ES, Orlicky DJ, Jackman M, Maclean PS, Cain S, Crunk AE, Mansur A, Graham CE, Bowman TA, Greenberg AS.
Perilipin-2 Null Mice are Protected Against Diet-Induced Obesity, Adipose Inflammation and Fatty Liver Disease.
J Lipid Res. 2013

Non-Alcoholic Fatty Liver Disease:
Weston CJ, Shepherd EL, Claridge LC, Rantakari P, Curbishley SM, Tomlinson JW, Hubscher SG, Reynolds GM, Aalto K, Anstee QM, Jalkanen S, Salmi M, Smith DJ, Day CP, Adams DH
Vascular adhesion protein-1 promotes liver inflammation and drives hepatic fibrosis.
J Clin Invest. 2014

Lipodystrophy:
Prieur X, Dollet L, Takahashi M, Nemani M, Pillot B, Le May C, Mounier C, Takigawa-Imamura H, Zelenika D, Matsuda F, Fève B, Capeau J, Lathrop M, Costet P, Cariou B, Magré J.
Thiazolidinediones partially reverse the metabolic disturbances observed in Bscl2/seipin-deficient mice.
Diabetologia. 2013

Hypoglycemia:
Martin J, Maurhofer O, Bellance N, Benard G, Graber F, Hahn D, Galinier A, Hora C, Gupta A, Ferrand G, Hoppeler H, Rossignol R, Dufour JF, St-Pierre MV.
Disruption of the histidine triad nucleotide-binding hint2 gene in mice affects glycemic control and mitochondrial function.
Hepatology. 2012

McArdle's Disease:
Nogales-Gadea G, Pinós T, Lucia A, Arenas J, Camara Y, Brull A, de Luna N, Martín MA, Garcia-Arumí E, Martí R, Andreu AL.
Knock-in mice for the R50X mutation in the PYGM gene present with McArdle disease.
Brain. 2012

Lafora Disease:
Duran J, Tevy MF, Garcia-Rocha M, Calbó J, Milán M, Guinovart JJ.
Deleterious effects of neuronal accumulation of glycogen in flies and mice.
EMBO Mol Med. 2012

Bone-mineral metabolic disorders:
David V, Martin A, Hedge AM, Rowe PS.
Matrix extracellular phosphoglycoprotein (MEPE) is a new bone renal hormone and vascularization modulator.
Endocrinology. 2009

Milk production abrogation:
Andreas F. Kolb, Reinhard C. Huber, Simon G. Lillico, Ailsa Carlisle, Claire J. Robinson, Claire Neil, Linda Petrie, Dorte B. Sorensen, I. Anna S. Olsson, C. Bruce A. Whitelaw.
Milk Lacking α-Casein Leads to Permanent Reduction in Body Size in Mice.
PlosOne. 2011

Model Creation Services

Conditional Knockout (Learn more):
Qvartskhava N, Lang PA, Görg B, Pozdeev VI, Ortiz MP, Lang KS, Bidmon HJ, Lang E, Leibrock CB, Herebian D, Bode JG, Lang F, Häussinger D.
Hyperammonemia in gene-targeted mice lacking functional hepatic glutamine synthetase.
Proc Natl Acad Sci U S A. 2015

Li LC, Wang Y, Carr R, Haddad CS, Li Z, Qian L, Oberholzer J, Maker AV, Wang Q, Prabhakar BS
IG20/MADD Plays a Critical Role in Glucose-Induced Insulin Secretion.
Diabetes. 2014

da Silva Xavier G, Mondragon A, Sun G, Chen L, McGinty JA, French PM, Rutter GA.
Abnormal glucose tolerance and insulin secretion in pancreas-specific Tcf7l2-null mice.
Diabetologia. 2012

Constitutive Knockout (Learn more):
Solberg A, Robertson AB, Aronsen JM, Rognmo O, Sjaastad I, Wisløff U, Klungland A.
Deletion of mouse Alkbh7 leads to obesity.
J Mol Cell Biol. 2013

Safe Knockout (Learn more):
McManaman JL, Bales ES, Orlicky DJ, Jackman M, Maclean PS, Cain S, Crunk AE, Mansur A, Graham CE, Bowman TA, Greenberg AS.
Perilipin-2 Null Mice are Protected Against Diet-Induced Obesity, Adipose Inflammation and Fatty Liver Disease.
J Lipid Res. 2013

Humanization Knockin (Learn more):
Chen J, Kaiyala KJ, Lam J, Agrawal N, Nguyen L, Ogimoto K, Spencer D, Morton GJ, Schwartz MW, Dichek HL.
In vivo structure-function studies of human hepatic lipase: the catalytic function rescues the lean phenotype of HL-deficient (hl-/-) mice.
Physiol Rep. 2015

Point Mutation Knockin (Learn more):
Winnay JN, Solheim MH, Dirice E, Sakaguchi M, Noh HL, Kang HJ, Takahashi H, Chudasama KK, Kim JK, Molven A, Kahn CR, Njølstad PR.
PI3-kinase mutation linked to insulin and growth factor resistance in vivo.
J Clin Invest. 2016

Nogales-Gadea G, Pinós T, Lucia A, Arenas J, Camara Y, Brull A, de Luna N, Martín MA, Garcia-Arumí E, Martí R, Andreu AL.
Knock-in mice for the R50X mutation in the PYGM gene present with McArdle disease.
Brain. 2012

Permissive Locus HPRT Knockin (Learn more):
Villarroel-Espíndola F, Maldonado R, Mancilla H, Vander Stelt K, Acuña A, Covarrubias A, López C, Angulo C, Castro MA, Slebe JC, Durán J, García-Rocha M, Guinovart JJ, Concha II.
Muscle glycogen synthase isoform is responsible for testicular glycogen synthesis: Glycogen overproduction induces apoptosis in male germ cells.
J Cell Biochem. 2013

Reporter Knockin (Learn more):
Lengacher S, Nehiri-Sitayeb T, Steiner N, Carneiro L, Favrod C, Preitner F, Thorens B, Stehle JC, Dix L, Pralong F, Magistretti PJ, Pellerin L.
Resistance to diet-induced obesity and associated metabolic perturbations in haploinsufficient monocarboxylate transporter 1 mice.
PLoS One. 2013