RGD Reference Report - Genetic dissection of Iddm26 in the spontaneously diabetic BBDP rat. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Genetic dissection of Iddm26 in the spontaneously diabetic BBDP rat.

Authors: Sarmiento, J  Wallis, RH  Ning, T  Marandi, L  Chao, GY  Paterson, AD  Poussier, P 
Citation: Sarmiento J, etal., Genes Immun. 2014 Sep;15(6):378-91. doi: 10.1038/gene.2014.29. Epub 2014 Jun 12.
RGD ID: 10043114
Pubmed: PMID:24920533   (View Abstract at PubMed)
DOI: DOI:10.1038/gene.2014.29   (Journal Full-text)

The 40 Mb T1D susceptibility locus Iddm26 was mapped to chromosome 2 through linkage analysis of a conditioned cross-intercross between the diabetes-prone BBDP and the diabetes-resistant ACI.BBDP-Iddm1,Iddm2 (ACI.1u.Lyp). It is flanked by Iddm32 and Iddm33, which control the kinetics of disease progression. To fine-map Iddm26 and characterize immune phenotypes controlled by this locus, several congenic sublines were generated carrying smaller, overlapping intervals spanning Iddm26 and fragments of Iddm32 and 33. Analysis of disease susceptibility, age of disease onset, and immune phenotypes in these sublines identified subloci regulating these different parameters. Two ACI.1u.Lyp-derived subloci, Iddm26.1 and Iddm26.2, imparted significant protection from diabetes, decreasing the cumulative incidence by as much as 57% and 28%, respectively. Iddm26.2, which overlaps with the human PTPN22 locus, only affected disease susceptibility, whereas Iddm26.1 also significantly affected disease kinetics, delaying T1D onset by more than 10 days compared with the parental BBDP strain. These Iddm26 subloci also regulated various immune phenotypes, including the proportion of splenic macrophages by Iddm26.1, and the proportion of activated T-cells in secondary lymphoid organs by Iddm26.2. The analysis of Iddm26 congenic animals in two different SPF facilities demonstrated that the influence of this locus on T1D is environment-dependent.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ACI.BBDP-(RT1u)(Gimap5)/SunnRattype 1 diabetes mellitus MODEL: controlIAGP compared to BBDP/WorSunnRGD 
BBDP.ACI-(D2Mit8-D2Arb16)(D2Rat354-D2Rat69)/SunnRattype 1 diabetes mellitus onsetIAGP compared to BBDP/WorSunn and BBDP.ACI-(D2Mit8-D2Rat69)/SunnRGD 
BBDP.ACI-(D2Mit8-D2Arb16)/SunnRattype 1 diabetes mellitus onsetIAGP compared to BBDP/WorSunnRGD 
BBDP.ACI-(D2Mit8-D2Rat354)/SunnRattype 1 diabetes mellitus onsetIAGP compared to BBDP/WorSunnRGD 
BBDP.ACI-(D2Mit8-D2Rat69)/SunnRattype 1 diabetes mellitus onsetIAGP compared to BBDP/WorSunn and BBDP.ACI-(D2Mit8-D2Arb16)(D2Rat354-D2Rat69)/SunnRGD 
BBDP.ACI-(D2Rat50-D2Rat63)/SunnRattype 1 diabetes mellitus onsetIAGP compared to BBDP/WorSunnRGD 
BBDP/WorSunnRattype 1 diabetes mellitus MODEL: spontaneousIAGP compared to ACI and ACI.BBDP-(RT1u)(Gimap5)/SunnRGD 
Iddm54Rattype 1 diabetes mellitus susceptibilityIAGP  RGD 
Iddm55Rattype 1 diabetes mellitus susceptibilityIAGP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BBDP.ACI-(D2Arb16-D2Rat63)/SunnRatdecreased CD4-positive, CD25-positive, alpha-beta regulatory T cell number  IAGP compared to BBDP/WorSunnRGD 
BBDP.ACI-(D2Mit8-D2Rat354)/SunnRatdecreased CD4-positive, CD25-positive, alpha-beta regulatory T cell number  IAGP compared to BBDP/WorSunnRGD 
BBDP.ACI-(D2Arb16-D2Rat63)/SunnRatdecreased IgE level  IAGP compared to BBDP/WorSunnRGD 
BBDP.ACI-(D2Mit8-D2Arb16)(D2Rat354-D2Rat69)/SunnRatdecreased IgE level  IAGP compared to BBDP/WorSunnRGD 
BBDP.ACI-(D2Mit8-D2Arb16)/SunnRatdecreased IgE level  IAGP compared to BBDP/WorSunnRGD 
BBDP.ACI-(D2Mit8-D2Rat354)/SunnRatdecreased IgE level  IAGP compared to BBDP/WorSunnRGD 
BBDP.ACI-(D2Mit8-D2Rat69)/SunnRatdecreased IgE level  IAGP compared to BBDP/WorSunnRGD 
BBDP.ACI-(D2Rat50-D2Rat63)/SunnRatdecreased IgE level  IAGP compared to BBDP/WorSunnRGD 
BBDP.ACI-(D2Mit8-D2Arb16)/SunnRatdecreased macrophage cell number  IAGP compared to BBDP/WorSunn and spleenRGD 
BBDP.ACI-(D2Mit8-D2Rat354)/SunnRatdecreased macrophage cell number  IAGP compared to BBDP/WorSunn and spleenRGD 
BBDP.ACI-(D2Arb16-D2Rat63)/SunnRatdecreased susceptibility to autoimmune diabetes  IAGP compared to BBDP/WorSunnRGD 
BBDP.ACI-(D2Mit8-D2Arb16)/SunnRatdecreased susceptibility to autoimmune diabetes  IAGP compared to BBDP/WorSunnRGD 
BBDP.ACI-(D2Mit8-D2Rat354)/SunnRatdecreased susceptibility to autoimmune diabetes  IAGP compared to BBDP/WorSunnRGD 
BBDP.ACI-(D2Mit8-D2Arb16)(D2Rat354-D2Rat69)/SunnRatincreased CD4-positive, CD25-positive, alpha-beta regulatory T cell number  IAGP compared to BBDP/WorSunnRGD 
Iddm54Ratincreased circulating glucose level susceptibilityIAGP  RGD 
Iddm55Ratincreased circulating glucose level susceptibilityIAGP  RGD 
BBDP/WorSunnRatincreased IgE level  IAGP compared to congenic strainsRGD 
BBDP.ACI-(D2Arb16-D2Rat63)/SunnRatincreased macrophage cell number  IAGP compared to ACI.BBDP-RT1uGimap5/Sunn and spleenRGD 
BBDP.ACI-(D2Mit8-D2Arb16)(D2Rat354-D2Rat69)/SunnRatincreased macrophage cell number  IAGP compared to ACI.BBDP-RT1uGimap5/Sunn and spleenRGD 
BBDP.ACI-(D2Mit8-D2Rat69)/SunnRatincreased macrophage cell number  IAGP compared to ACI.BBDP-RT1uGimap5/Sunn and spleenRGD 
BBDP.ACI-(D2Rat50-D2Rat63)/SunnRatincreased macrophage cell number  IAGP compared to ACI.BBDP-RT1uGimap5/Sunn and spleenRGD 
BBDP/WorSunnRatincreased macrophage cell number  IAGP compared to ACI.BBDP-RT1uGimap5/Sunn and spleenRGD 
Iddm54Ratincreased urine glucose level susceptibilityIAGP  RGD 
Iddm55Ratincreased urine glucose level susceptibilityIAGP  RGD 
BBDP.ACI-(D2Mit8-D2Arb16)(D2Rat354-D2Rat69)/SunnRatthymus hyperplasia  IAGP compared to ACI.BBDP-RT1uGimap5/SunnRGD 
BBDP.ACI-(D2Mit8-D2Arb16)/SunnRatthymus hyperplasia  IAGP compared to ACI.BBDP-RT1uGimap5/SunnRGD 
BBDP.ACI-(D2Mit8-D2Rat354)/SunnRatthymus hyperplasia  IAGP compared to ACI.BBDP-RT1uGimap5/SunnRGD 
BBDP.ACI-(D2Rat50-D2Rat63)/SunnRatthymus hyperplasia  IAGP compared to ACI.BBDP-RT1uGimap5/SunnRGD 
BBDP/WorSunnRatthymus hyperplasia  IAGP compared to ACI.BBDP-RT1uGimap5/SunnRGD 
BBDP.ACI-(D2Arb16-D2Rat63)/SunnRatthymus hypoplasia  IAGP compared to BBDP/WorSunnRGD 
BBDP.ACI-(D2Mit8-D2Rat69)/SunnRatthymus hypoplasia  IAGP compared to BBDP/WorSunnRGD 
Objects referenced in this article
QTL Iddm26 Insulin dependent diabetes mellitus QTL 26 Rattus norvegicus

Additional Information