RGD Reference Report - Non-major histocompatibility complex-linked diabetes susceptibility loci on chromosomes 4 and 13 in a backcross of the DP-BB/Wor rat to the WF rat. - Rat Genome Database

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Non-major histocompatibility complex-linked diabetes susceptibility loci on chromosomes 4 and 13 in a backcross of the DP-BB/Wor rat to the WF rat.

Authors: Martin, AM  Blankenhorn, EP  Maxson, MN  Zhao, M  Leif, J  Mordes, JP  Greiner, DL 
Citation: Martin AM, etal., Diabetes 1999 Jan;48(1):50-8
RGD ID: 61480
Pubmed: PMID:9892222   (View Abstract at PubMed)

BB rats are used as models of autoimmune human IDDM. Genetic control of IDDM in both species is complex, including both major histocompatibility complex (MHC)-linked and non-MHC-linked genes. DP-BB rats develop IDDM spontaneously. Expression of disease in these animals requires homozygosity at the lyp locus, which causes lymphopenia. All genetic analyses of BB rat diabetes to date have backcrossed to the DP-BB strain or used (DP-BB x non-BB)F2 animals to ensure that a fraction of progeny are homozygous for lyp. Here we report the analysis of a backcross of the DP-BB rat to the histocompatible WF rat. Neither WF nor (WF x DP-BB)F1 animals develop spontaneous IDDM. However, 95% of (WF x DP-BB)F1 rats and a fraction of (WF x DP-BB) x WF backcross animals readily develop IDDM after treatment with polyinosinic:polycytidylic acid and a cytotoxic anti-RT6.1 monoclonal antibody. Using simple sequence length polymorphism analysis, we have mapped loci on chromosomes 4 and 13 that show significant linkage to IDDM expression and insulitis. The susceptibility locus on chromosome 4 is linked to, but not identical to, lyp. We propose a disease model for the BB rat that requires 1) the RT1u MHC haplotype for disease susceptibility, 2) a new locus on chromosome 4 for disease initiation (as measured by insulitis), 3) a new locus on chromosome 13 for disease progression in response to environmental perturbation, and 4) lyp for spontaneous expression of disease.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Iddm11RatChronic Pancreatitis  IDA  RGD 
Iddm11RatExperimental Diabetes Mellitus  IDA  RGD 
Iddm12RatExperimental Diabetes Mellitus  IDA  RGD 
Iddm13RatExperimental Diabetes Mellitus  IDA  RGD 
Iddm8RatExperimental Diabetes Mellitus  IDA  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Iddm11Ratincreased circulating glucose level  QTM  RGD 
Iddm12Ratincreased circulating glucose level  QTM  RGD 
Iddm13Ratincreased circulating glucose level  QTM  RGD 
Iddm11Ratinsulitis  IDA  RGD 
Iddm11Ratpancreas inflammation  QTM  RGD 
Objects Annotated

Iddm11  (Insulin dependent diabetes mellitus QTL 11)
Iddm12  (Insulin dependent diabetes mellitus QTL 12)
Iddm13  (Insulin dependent diabetes mellitus QTL 13)
Iddm8  (Insulin dependent diabetes mellitus QTL 8)

BBDP/WorBrm  (NA)
WF/CrCrl  (NA)

Objects referenced in this article
Strain BBDP/Rhw null Rattus norvegicus
Strain BBDR/WorBrm null Rattus norvegicus
QTL Iddm14 Insulin dependent diabetes mellitus QTL 14 Rattus norvegicus
Strain WF Wistar Furth Rattus norvegicus
Strain WF/Pit Wistar Furth Rattus norvegicus

Additional Information