Potential of gene therapy for restoration of endocrine thymic function in thymus-deficient animal models

BRAVO MARGARITA GARCIA DE; POLO, MONICA; REGGIANI, PAULA; GALASSI, PABLO,; RIMOLDI, OMAR; GOYA, RODOLFO

Mar del Plata 17-20 de noviembre

Congreso; XLIII Reuni¨®n Anual de SAIB; 2007

Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular

  METABOLIC ALTERATIONS IN CONGENITALLY ATHYMIC MALE MICE: EFFECTS OF NEONATAL THYMULIN GENE THERAPY Bravo, Margarita G. de, Polo M¨®nica, Reggiani Paula, Galassi Pablo, Rimoldi Omar and Goya Rodolfo INIBIOLP (UNLP-CONICET) Facultad de Cs. M¨¦dicas. La Plata Key Words: ATHYMIC MICE, LIPIDS, THYMULIN, GENE THERAPY Adult congenitally athymic (nude) mice display endocrine imbalances and a moderate hyperglycemia. Here we determined the impact of congenital athymia on lipid and glucose plasma  levels as well as on hepatic lipid composition in male nude mice. We also assessed the ability of neonatal thymulin gene therapy (NTGT) to prevent the metabolic effects of athymia. An adenoviral vector, RAd-metFTS, expressing a synthetic DNA sequence encoding the thymic peptide thymulin was used. On postnatal day 1-2 nu/nu and nu/+ mice were i.m. injected with 108 pfu RAdmetFTS or RAd-¦Âgal (control vector). The animals were processed at 71 days of age. Circulating thymulin, glucose, cholesterol (CHOL) and triacylglycerides (TAG) as well as hepatic TAG, phospholipid (PL) fatty acid composition and free, esterified and microsomal CHOL was determined. The nu/nu controls were moderately hyperglycemic when compared with their nu/+ counterparts (109.4¡À11.8 vs. 87¡À5.0; P<0.05). NTGT fully prevented hyperglycemia in nu/nu mice. Athymic males showed significantly reduced levels of plasma CHOL and TAG, alterations that were not prevented by NTGT. Hepatic levels of TAG were reduced in control nu/nu but this alteration was prevented by NTGT. We conclude that adult nu/nu mice develop multiple alterations in lipid and glucose metabolism. Thymulin may modulate some of these metabolic variables, notably glucose homeostasis.