Animal Models for Insulin-Dependent Diabetes Mellitus

Bieg, Sabine; Lernmark, Åke

doi:10.1007/978-1-59259-704-8_5

Cited by 4 publications

(12 citation statements)

References 211 publications

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“…In this study, we focused on the detailed histopathology and immunopathology of the endocrine and exocrine pancreas and a number of other organs, such as the thyroid and the adrenals, which may potentially be involved in the autoimmune process. This systematic investigation allows a comparison with other animal models of human T1DM, such as the diabetes of the BB rat and the NOD mouse [3,18] and may help to clarify the specificity of the immune-mediated attack on the beta cells.…”

Section: Introductionmentioning

confidence: 99%

Pathology of the pancreas and other organs in the diabetic LEW.1AR1/Ztm- iddm rat, a new model of spontaneous insulin-dependent diabetes mellitus

et al. 2004

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We studied the histo- and immunopathology of the endocrine and exocrine pancreas and a number of other organs in a new insulin-dependent diabetes mellitus (IDDM) rat model (LEW.1AR1/Ztm- iddm rat). The pancreas of the acutely diabetic animals showed an inflammatory infiltrate, involving all islets and ducts. The islet infiltrate was composed mainly of ED1-positive macrophages and T lymphocytes, comprising a large number of CD8(+) lymphocytes and a few CD4(+) lymphocytes. In addition, the islets displayed apoptotic cells, characterized by condensation and fragmentation of nuclear chromatin. These cells were identified as beta cells by insulin immunostaining. Other endocrine and exocrine glands, including adrenals and thyroid, as well as salivary and submandibular glands, were unaffected. Organs from the digestive tract or systemic circulatory system, including small intestine, liver, heart, and lung also showed no involvement. The kidney was intact in acutely diabetic rats. However, 6 months after diabetes manifestation, pathological changes compatible with a diabetic nephropathy had developed, affecting both the glomerula and the proximal tubular segments. It was concluded that the autoimmune process in this new IDDM rat model is restricted to the endocrine pancreas and leads to apoptotic beta cell destruction.

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Section: Introductionmentioning

confidence: 99%

Pathology of the pancreas and other organs in the diabetic LEW.1AR1/Ztm- iddm rat, a new model of spontaneous insulin-dependent diabetes mellitus

et al. 2004

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“…Diabetes in the BB rat is associated with autoimmunity not only to the pancreatic islet cells but also to other endocrine organ [1]; BB rats were found positive for autoantibodies to gastric parietal cells, thyroid colloid antigens, smooth muscle cells and thymocytes [2,3]. The genetic susceptibility to autoimmune diseases is notoriously complex; however, the BB rat has proven to be a very useful model to dissect the genetics of organ specific autoimmunity [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Genetic dissection of lymphopenia from autoimmunity by introgression of mutated Ian5 gene onto the F344 rat

Moralejo

Park

Speros

et al. 2003

Journal of Autoimmunity

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Peripheral T cell lymphopenia (lyp) in the BioBreeding (BB) rat is linked to a frameshift mutation in Ian5, a member of the Immune Associated Nucleotide (Ian) gene family on rat chromosome 4. This lymphopenia leads to type 1 (insulin-dependent) diabetes mellitus (T1DM) at rates up to 100% when combined with the BB rat MHC RT1 u/u genotype. In order, to better study the lymphopenia phenotype without possible confounding effects of diabetes or other autoimmune disease, we generated congenic F344.lyp rats by introgression of lyp on diabetes-resistant MHC RT1 lv1/lv1 F344 rats. Analysis of thymic CD4 and CD8 T lymphocytes revealed no difference in the percentage of CD4(-)CD8(+)and CD4(+)CD8(-)subsets in lyp/lyp compared to +/+ F344 rats. The same subsets was however dramatically reduced in blood (P=0.005), spleen (P=0.019) and mesenteric lymph nodes (MLN) (P<0.0001). Compared to F344 +/+ rats double positive CD4(+)CD8(+)T cells were increased only in lyp/lyp spleen (P=0.034) while double negative CD4(-)CD8(-)were increased in thymus (P=0.033), spleen (P=0.012), MLN (P<0.0001), and peripheral blood (P<0.0001). There were no signs of inflammatory lesions in organs and tissues in F344.lyp/lyp rats examined at 120 days of age or older. We thus conclude that the lymphopenia phenotype was reconstituted by introgression of lyp on to F344 rats without subsequent development of organ-specific autoimmunity. The congenic F344.lyp rat should prove useful to dissect the mechanisms by which the Ian5 frameshift mutation affects T cell selection, differentiation and maturation without organ-specific autoimmunity.

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“…A incidência cumulativa de diabetes nestes ratos pode ser de 100% se mantidos em ambiente livre de patógenos. 18 As manifestações incluem hipoinsulinemia, hiperglicemia (20 a 30mmol/L), glicosúria, perda de peso, polidipsia, poliúria e cetoacidose. Tem-se reportado tratamentos aplicados a estes ratos que interferem na resposta imunológica e previnem o diabetes, como timectomia neonatal, irradiação linfóide total, tratamento com soro antilinfocítico ou ciclosporina.…”

Section: Diabetes Experimental Espontâneounclassified

Modelos experimentais para o estudo do diabetes tipo 1

Kirsten

Sesterheim

Saitovitch

2010

Medicina (Ribeirão Preto)

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Os modelos animais de diabetes têm sido usados extensivamente na obtenção do esclarecimentosobre esta doença. O objetivo deste estudo foi realizar uma revisão bibliográfica sobre os principaismodelos experimentais para o estudo do diabetes mellitus. Dentre os modelos experimentais para oestudo do diabetes, existem os modelos induzidos quimicamente por aloxana e streptozotocina, sendoque a dose utilizada depende da espécie do animal e do seu peso. Além disso, existem dois excelentesmodelos de diabetes espontâneo: os ratos BB (Biobreading) e os camundongos NOD (Non ObeseDiabetic). Os camundongos NOD são o modelo mais estudado de doença espontânea auto-imuneórgão-específico em todo o mundo. As razões para a preferência deste modelo incluem um genomabem definido, maior quantidade de reagentes monoclonais para a análise de componentes do sistemaimune e um custo razoavelmente baixo, comparado com a utilização de ratos. Estes camundongosexibem autoimunidade espontânea com destruição das ilhotas pancreáticas, de forma semelhante àobservada em humanos. A destruição auto-imune é caracterizada por insulite e infiltrado leucocitárionas ilhotas pancreáticas. Esta infiltração é composta predominantemente por células dendríticas, macrófagos,por células TCD4, TCD8 e células B. Os fatores ambientais em conjunto com a genética,claramente modificam a incidência do diabetes tipo 1 nos modelos experimentais espontâneos. Asuscetibilidade destes camundongos é poligênica e ambiental, enfatizando condições de habitação,sanitárias, dietéticas e de gênero. A incidência de diabetes em camundongos NOD é aproximadamentequatro vezes maior em fêmeas do que em machos. As informações obtidas através deste excelentemodelo animal podem ser relevantes para O entendimento do processo da doença nos humanos.

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Animal Models for Insulin-Dependent Diabetes Mellitus

Cited by 4 publications

References 211 publications

Pathology of the pancreas and other organs in the diabetic LEW.1AR1/Ztm- iddm rat, a new model of spontaneous insulin-dependent diabetes mellitus

Pathology of the pancreas and other organs in the diabetic LEW.1AR1/Ztm- iddm rat, a new model of spontaneous insulin-dependent diabetes mellitus

Genetic dissection of lymphopenia from autoimmunity by introgression of mutated Ian5 gene onto the F344 rat

Modelos experimentais para o estudo do diabetes tipo 1

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