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Genetic control of non obese diabetic mice susceptibility to high-dose streptozotocin-induced diabetes

GONZALEZ, C ; CUVELLIER, S ; HUE-BEAUVAIS, C ; LEVI-STRAUSS, M

Diabetologia, 2003-09, Vol.46 (9), p.1291-1295 [Periódico revisado por pares]

Berlin: Springer

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Título:
Genetic control of non obese diabetic mice susceptibility to high-dose streptozotocin-induced diabetes
Autor: GONZALEZ, C ; CUVELLIER, S ; HUE-BEAUVAIS, C ; LEVI-STRAUSS, M
Assuntos: Animals ; Biological and medical sciences ; Blood Glucose - metabolism ; Chromosome Mapping ; Crosses, Genetic ; Diabetes Mellitus, Experimental - genetics ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Genetic Markers ; Genetic Predisposition to Disease - genetics ; Genome ; Genotype ; Kinetics ; Medical sciences ; Metabolic diseases ; Mice ; Mice, Inbred C3H - genetics ; Mice, Inbred NOD - genetics ; Obesity ; Species Specificity ; Time Factors
É parte de: Diabetologia, 2003-09, Vol.46 (9), p.1291-1295
Descrição: Streptozotocin is a monofunctional alkylating agent that induces diabetes in a large variety of mammals. While multiple low doses of streptozotocin induce immune-mediated diabetes, a single high dose of streptozotocin causes a strictly toxic diabetes. Among mouse strains, non-obese diabetic (NOD) mice are characterized by an extreme susceptibility to high dose of streptozotocin-induced diabetes whereas C3H/Or mice are particularly resistant. We hypothesized that NOD genes involved in high dose streptozotocin-induced diabetes could be also involved in the autoimmune destruction of pancreatic beta cells that characterizes this mouse strain which is a model of Type 1 diabetes. We carried out a whole genome linkage scan on a population of (C3H/Or x NOD) x NOD backcross 1 mice in order to identify the genetic loci involved in NOD susceptibility to high dose of streptozotocin-induced diabetes. Two loci, in chromosome 9 (D9Mit135 marker, 48 cM) and in chromosome 11 (D11Mit286 marker, 52 cM), were associated with NOD susceptibility to high dose streptozotocin-induced diabetes, the latter being co-localized with the autoimmune diabetes-predisposing idd4 locus. Moreover, we report here that C57BL/6 mice deficient in Nitric Oxide Synthase 2 were as sensitive as wild-type C57BL/6 mice to high dose streptozotocin-induced diabetes. Although the Nitric Oxide Synthase 2 ( Nos2) gene, localized at 45.6 cM in chromosome 11, is a good candidate gene, our results suggest that Nitric Oxide Synthase 2 activation might not be a crucial event for streptozotocin-induced destruction of pancreatic beta cells.
Editor: Berlin: Springer
Idioma: Inglês

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Genetic control of non obese diabetic mice susceptibility to high-dose streptozotocin-induced diabetes

GONZALEZ, C ; CUVELLIER, S ; HUE-BEAUVAIS, C ; LEVI-STRAUSS, M

Berlin: Springer

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