RGD Reference Report - Identification of a major locus for islet inflammation and fibrosis in the Spontaneously Diabetic Torii rat. - Rat Genome Database

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Identification of a major locus for islet inflammation and fibrosis in the Spontaneously Diabetic Torii rat.

Authors: Fuse, M  Yokoi, N  Shinohara, M  Masuyama, T  Kitazawa, R  Kitazawa, S  Seino, S 
Citation: Fuse M, etal., Physiol Genomics. 2008 Jul 8;.
RGD ID: 2298688
Pubmed: (View Article at PubMed) PMID:18612083
DOI: Full-text: DOI:10.1152/physiolgenomics.90214.2008

The pathogenesis of inflammation and fibrosis in the pancreatic islets in diabetes is largely unknown. Spontaneously Diabetic Torii (SDT) rats exhibit inflammation and fibrosis in and around the islets during the development of the disease. We investigated genetic factors for diabetes, islet inflammation, and fibrosis in the SDT rat. We produced F1 and F2 rats by intercross between SDT and F344 rats, and examined the onset of diabetes, glucose tolerance, and histology of the pancreas, and performed genetic analysis of these traits. We then established a congenic strain carrying the SDT allele at the strongest diabetogenic locus on the F344 genetic background, and characterized glucose tolerance and histology of the pancreas. F1 rats showed glucose intolerance and inflammatory changes mainly in the islets. Genetic analysis of diabetes identified a major locus on chromosome 3, designated Dmsdt1, at which a dominantly acting SDT allele was involved. Quantitative trait locus (QTL) analysis of glucose tolerance revealed, in addition to Dmsdt1 (logarithm of odds [LOD] 5.3 near D3Mit12), three other loci, designated Dmsdt2 (LOD 4.2 at D8Rat46), Dmsdt3 (LOD 3.8 near D13Arb5), and Dmsdt4 (LOD 5.8 at D14Arb18). Analysis of a congenic strain for Dmsdt1 indicates that the dominantly acting SDT allele induces islet inflammation and fibrosis. Thus, we have found a major locus on chromosome 3 for islet inflammation and fibrosis in the SDT rat. Identification of the genes responsible should provide insight into the pathogenesis of diabetes. Key words: congenic, diabetes, genetic factor, glucose tolerance.

Disease Annotations    
diabetes mellitus  (IAGP)
obesity  (IAGP)

Phenotype Annotations    

Mammalian Phenotype

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Objects Annotated

Bw82  (Body weight QTL 82)
Gluco35  (Glucose level QTL 35)
Gluco36  (Glucose level QTL 36)
Gluco37  (Glucose level QTL 37)
Gluco38  (Glucose level QTL 38)

Objects referenced in this article
QTL Bw117 Body weight QTL 117 Rattus norvegicus
QTL Bw24 Body weight QTL 24 Rattus norvegicus
QTL Bw31 Body weight QTL 31 Rattus norvegicus
QTL Bw36 Body weight QTL 36 Rattus norvegicus
QTL Bw5 Body weight QTL5 Rattus norvegicus
Strain F344-Chr 3SDT/Nyo null Rattus norvegicus
QTL Gluco39 Glucose level QTL 39 Rattus norvegicus
QTL Niddm21 Non-insulin dependent diabetes mellitus QTL 21 Rattus norvegicus
QTL Pia6 Pristane induced arthritis QTL 6 Rattus norvegicus

Additional Information