Transgenic animal models and gene therapy approaches for diabetes
Centre de Biotecnologia Animal i Teràpia Gènica, Universitat Autònoma de Barcelona
http://cbateg.uab.cat

Principal Investigator Fàtima Bosch fatima.bosch@uab.cat Associate researchers Ana Carretero, Tura Ferré, Sylvie Franckhauser, Miquel García, Xavier Leon, Maria Molas, Sergio Antonio Muñoz, Víctor Nacher, Marc Navarro, Pedro José Otaegui, Anna Pujol, Martí Pumarola, Efren Riu, Jesús Ruberte, Virginia Haurigot Postdoctoral fellows Eduard Ayuso, Alba Casellas, Judith Agudo, Laia Vilà, Ricardo Lage, Ivel Elias, Verónica Jiménez PhD students David Callejas, Albert Ribera, Carles Roca, Albert Ruzo, Pilar Villacampa, Meritxell Morró, Cristina Mallol, Iris Grifoll, Sara Marcó Lab technicians Jennifer Barrero, Marta Moya, Mireia Zaguirre Administrative staff Montse Bellido

Palabras clave
Beta-cell signal transduction. Gene therapy. Insulin sensitivity and resistance. Retinopathy.

Principales líneas de investigación
The study of the causes and pathophysiological mechanisms of diabetes mellitus using transgenic animal models.
Analysis of the role of metabolic pathways in the development of insulin resistance and obesity, and the investigation of the molecular mechanisms involved in secondary complications (retinopathy, neuropathy).
The development of new gene-therapy approaches for the treatment of diabetes mellitus based:
a) on the manipulation of skeletal muscle and the liver to increase glucose uptake, and
b) on engineering the endocrine pancreas in vivo to regenerate beta cell mass.

Publicaciones
Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance
Liew CW, Boucher J, Cheong JK, Vernochet C, Koh HJ, Mallol C, Townsend K, Langin D, Kawamori D, Hu J, Tseng YH, Hellerstein MK, Farmer SR, Goodyear L, Doria A, Blüher M, Hsu SI, Kulkarni RN
Nat Med, doi:10.1038/nm.3056 (2013)
Article

Nonviral-mediated hepatic expression of IGF-I increases Treg levels and suppresses autoimmune diabetes in mice
Anguela XM, Tafuro S, Roca C, Callejas D, Agudo J, Obach M, Ribera A, Ruzo A, Mann CJ, Casellas A, Bosch F
Diabetes, 62, 551-560 (2013)
Article

Adipose Tissue Overexpression of Vascular Endothelial Growth Factor Protects Against Diet-Induced Obesity and Insulin Resistance
Elias I, Franckhauser S, Ferré T, Vilà L, Tafuro S, Muñoz S, Roca C, Ramos D, Pujol A, Riu E, Ruberte J, Bosch F
Diabetes, 61, 1801-1813 (2012)
Article

Vascular Endothelial Growth Factor-Mediated Islet Hypervascularization and Inflammation Contribute to Progressive Reduction of β-Cell Mass
Agudo J, Ayuso E, Jimenez V, Casellas A, Mallol C, Salavert A, Tafuro S, Obach M, Ruzo A, Moya M, Pujol A, Bosch F
Diabetes, 61, 2851-2861 (2012)
Article

LRH-1-dependent glucose sensing determines intermediary metabolism in liver
Oosterveer MH, Mataki C, Yamamoto H, Harach T, Moullan N, van Dijk TH, Ayuso E, Bosch F, Postic C, Groen AK, Auwerx J, Schoonjans K
J Clin Invest, 122, 2817-2826 (2012)
Article

Protein kinase C delta (PKCδ) affects proliferation of insulin-secreting cells by promoting nuclear extrusion of the cell cycle inhibitor p21Cip1/WAF1
Ranta F, Leveringhaus J, Theilig D, Schulz-Raffelt G, Hennige AM, Hildebrand DG, Handrick R, Jendrossek V, Bosch F, Schulze-Osthoff K, Häring HU, Ullrich S
PLoS ONE, 6, e28828 (2011)
Publication

In vivo genetic engineering of murine pancreatic beta cells mediated by single-stranded adeno-associated viral vectors of serotypes 6, 8 and 9
Jimenez V, Ayuso E, Mallol C, Agudo J, Casellas A, Obach M, Muñoz S, Salavert A, Bosch F
Diabetologia, 54, 1075-1086 (2011)
Article

Molecular signature of the immune and tissue response to non-coding plasmid DNA in skeletal muscle after electrotransfer
Mann CJ, Anguela XM, Montané J, Obach M, Roca C, Ruzo A, Otaegui P, Mir LM, Bosch F
Gene Ther, doi 10.1038/gt.2011.198 (2011)
Article

Hypothalamic-specific manipulation of Fto, the ortholog of the human obesity gene FTO, affects food intake in rats
Tung YC, Ayuso E, Shan X, Bosch F, O'Rahilly S, Coll AP, Yeo GS
PLoS ONE, 5, e8771 (2010)

Diabetic neuropathy: electrophysiological and morphological study of peripheral nerve degeneration and regeneration in transgenic mice that express IFNbeta in beta cells
Serafín A, Molín J, Márquez M, Blasco E, Vidal E, Foradada L, Añor S, Rabanal RM, Fondevila D, Bosch F, Pumarola M
Muscle Nerve, 41, 630-641 (2010)

Overexpression of kinase-negative protein kinase Cdelta in pancreatic beta-cells protects mice from diet-induced glucose intolerance and beta-cell dysfunction
Hennige AM, Ranta F, Heinzelmann I, Düfer M, Michael D, Braumüller H, Lutz SZ, Lammers R, Drews G, Bosch F, Häring HU, Ullrich S
Diabetes, 59, 119-127 (2010)

High AAV vector purity results in serotype- and tissue-independent enhancement of transduction efficiency
Ayuso E, Mingozzi F, Montane J, Leon X, Anguela XM, Haurigot V, Edmonson SA, Africa L, Zhou S, High KA, Bosch F, Wright JF
Gene Ther, 17, 503-510 (2010)

The suppressor of cytokine signalling 2 (SOCS2) is a key repressor of insulin secretion
Lebrun P, Cognard E, Gontard P, Bellon-Paul R, Filloux C, Berthault MF, Magnan C, Ruberte J, Luppo M, Pujol A, Pachera N, Herchuelz A, Bosch F, Van Obberghen E
Diabetologia, 53, 1935-1946 (2010)

Chronically increased glucose uptake by adipose tissue leads to lactate production and improved insulin sensitivity rather than obesity in the mouse
Muñoz S, Franckhauser S, Elias I, Ferré T, Hidalgo A, Monteys AM, Molas M, Cerdán S, Pujol A, Ruberte J, Bosch F
Diabetologia, 53, 2417-2430 (2010)

Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age
Agudo J, Martin M, Roca C, Molas M, Bura AS, Zimmer A, Bosch F, Maldonado R
Diabetologia, 53, 2629-2640 (2010)

Production, purification and characterization of adeno-associated vectors
Ayuso E, Mingozzi F, Bosch F
Curr Gene Ther, 10, 423-436 (2010) Review

Skeletal muscle metabolism in the pathology and treatment of type 1 diabetes
Mann CJ, Ayuso E, Anguela XM, Bosch F
Curr Pharm Des, 16, 1002-1020 (2010) Review

Constitutive expression of suppressor of cytokine signalling-3 in skeletal muscle leads to reduced mobility and overweight in mice
Lebrun P, Cognard E, Bellon-Paul R, Gontard P, Filloux C, Jehl-Pietri C, Grimaldi P, Samson M, Pénicaud L, Ruberte J, Ferre T, Pujol A, Bosch F & Van Obberghen E
Diabetologia, 52, 2201-2212 (2009)

Increased intraocular insulin-like growth factor-I triggers blood-retinal barrier breakdown
Haurigot V, Villacampa P, Ribera A, Llombart C, Bosch A, Nacher V, Ramos D, Ayuso E, Segovia JC, Bueren JA, Ruberte J, Bosch F
J Biol Chem, 284, 22961-22969 (2009)

Scavenger function of resident autofluorescent perivascular macrophages and their contribution to the maintenance of the blood-retinal barrier
Mendes-Jorge L, Ramos D, Luppo M, Llombart C, Alexandre-Pires G, Nacher V, Melgarejo V, Correia M, Navarro M, Carretero A, Tafuro S, Rodriguez-Baeza A, Esperança-Pina JA, Bosch F, Ruberte J
Invest Ophthalmol Vis Sci, 50, 5997-6005 (2009)

IGF-1 mediates regeneration of endocrine pancreas by increasing beta-cell replication though cellcycle protein modulation in mice
Agudo J, Ayuso E, Jimenez V, Salavert A, Casellas A, Tafuro S, Haurigot V, Ruberte J, Segovia JC, Bueren J and Bosch F
Diabetologia, 51, 1862-1872 (2008)

Más información
2011 CIBERDEM Annual Report
2010 CIBERDEM Annual Report
2009 CIBERDEM Annual Report
2008 CIBERDEM Annual Report