RGD Reference Report - A novel Dock8 gene mutation confers diabetogenic susceptibility in the LEW.1AR1/Ztm-iddm rat, an animal model of human type 1 diabetes. - Rat Genome Database

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A novel Dock8 gene mutation confers diabetogenic susceptibility in the LEW.1AR1/Ztm-iddm rat, an animal model of human type 1 diabetes.

Authors: Arndt, T  Wedekind, D  Jorns, A  Tsiavaliaris, G  Cuppen, E  Hedrich, HJ  Lenzen, S 
Citation: Arndt T, etal., Diabetologia. 2015 Dec;58(12):2800-9. doi: 10.1007/s00125-015-3757-7. Epub 2015 Sep 12.
RGD ID: 11532657
Pubmed: PMID:26363782   (View Abstract at PubMed)
DOI: DOI:10.1007/s00125-015-3757-7   (Journal Full-text)

AIMS/HYPOTHESIS: The LEW.1AR1-iddm rat, an animal model of human type 1 diabetes, arose through a spontaneous mutation within the inbred strain LEW.1AR1. A susceptibility locus (Iddm8) on rat chromosome 1 (RNO1) has been identified previously, which is accompanied by autoimmune diabetes and the additional phenotype of a variable CD3(+) T cell frequency. METHODS: In the present study we characterised the Iddm8 region on RNO1 in backcross strains using the genetically divergent Brown Norway (BN) and Paris (PAR) rats. Candidate genes of the Iddm8 region were sequenced for mutation analysis. RESULTS: The Iddm8 region could be subdivided by single nucleotide polymorphism (SNP) analyses. In the first region, a mutation in exon 44 of the Dock8 gene was identified resulting in an amino acid exchange in the protein from glutamine to glutamate. This exchange is unique for the LEW.1AR1-iddm rat. In the second region, a SNP was detected in exon 11 of the Vwa2 gene with an exchange from arginine to tryptophan. This SNP is also present in other rat strains. CONCLUSIONS/INTERPRETATION: The Dock8 mutation gave rise to a new type 1 diabetes rat model with very close similarity to type 1 diabetes in humans, providing a deepened insight into the impact of genes involved in diabetes development.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DOCK8Humantype 1 diabetes mellitus  ISODock8 (Rattus norvegicus) RGD 
Dock8Mousetype 1 diabetes mellitus  ISODock8 (Rattus norvegicus) RGD 
Dock8Rattype 1 diabetes mellitus  IAGP  RGD 
Dock8m1ZtmRattype 1 diabetes mellitus  IAGP  RGD 
LEW.1AR1-iddm/ZtmRattype 1 diabetes mellitus MODEL: spontaneousIAGP  RGD 
LEW.1AR1/ZtmRattype 1 diabetes mellitus no_associationIAGP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dock8  (dedicator of cytokinesis 8)
Dock8m1Ztm  (dedicator of cytokinesis 8;mutant 1, Ztm)

Genes (Mus musculus)
Dock8  (dedicator of cytokinesis 8)

Genes (Homo sapiens)
DOCK8  (dedicator of cytokinesis 8)

LEW.1AR1-iddm/Ztm  (NA)
LEW.1AR1/Ztm  (NA)

Additional Information