RGD Reference Report - Genetic Dissection Reveals Diabetes Loci Proximal to the Gimap5 Lymphopenia Gene. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

Genetic Dissection Reveals Diabetes Loci Proximal to the Gimap5 Lymphopenia Gene.

Authors: Fuller, JM  Bogdani, M  Tupling, TD  Jensen, RA  Pefley, R  Manavi, S  Cort, L  Blankenhorn, EP  Mordes, JP  Lernmark, A  Kwitek, AE 
Citation: Fuller JM, etal., Physiol Genomics. 2009 Apr 7.
RGD ID: 2306526
Pubmed: PMID:19351909   (View Abstract at PubMed)
PMCID: PMC2696149   (View Article at PubMed Central)
DOI: DOI:10.1152/physiolgenomics.00015.2009   (Journal Full-text)

Congenic DRF.(f/f) rats are protected from type 1 diabetes (T1D) by 34 Mb of F344 DNA introgressed proximal to the Gimap5 lymphopenia gene. To dissect the genetic factor(s) that confer protection from T1D in the DRF.(f/f) rat line, DRF.(f/f) rats were crossed to inbred BBDR or DR.(lyp/lyp) rats to generate congenic sublines that were genotyped, monitored for T1D and positional candidate genes sequenced. All (100%) DR.(lyp/lyp) rats developed T1D by 83 days of age. Reduction of the DRF.(f/f) F344 DNA fragment by 26 Mb (42.52 Mb-68.51 Mb) retained complete T1D protection. Further dissection revealed that a 2 Mb interval of F344 DNA (67.41-70.17 Mb) (Region 1) resulted in 47% protection and significantly delayed onset (p<0.001 compared to DR.(lyp/lyp)). Retaining <1 Mb of F344 DNA at the distal end (76.49-76.83 Mb) (Region 2) resulted in 28% protection and also delayed onset (p<0.001 compared to DR.(lyp/lyp)). Comparative analysis of diabetes frequency in the DRF.(f/f) congenic sublines further refined the RNO4 Region 1 interval to approximately 670 Kb and Region 2 to the 340 Kb proximal to Gimap5. All congenic DRF.(f/f) sublines were prone to low-grade pancreatic mononuclear cell infiltration around ducts and vessels but less than 20% of islets in non-diabetic rats showed islet infiltration. Coding sequence analysis revealed TCR Vbeta 8E, 12 and 13 as candidate genes in Region 1 and Znf467 and Atp6v0e2 as candidate genes in Region 2. Our results show that spontaneous T1D is controlled by at least two genetic loci 7 Mb apart on rat chromosome 4. Key words: Type 1 diabetes, BB rat, T cell receptor, autoimmune.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRatlymphopenia  IAGP compared to BBDR/RhwRGD 
BBDR.F344-(D4Arb11-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRatlymphopenia  IAGP compared to BBDR.F344-(D4Rat153-D4Rhw8) and BBDP-(D4Rhw6-D4Rat62)/RhwRGD 
BBDR.F344-(D4Got33-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatlymphopenia  IAGP compared to BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRGD 
BBDR.F344-(D4Got59-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatlymphopenia  IAGP compared to BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRGD 
BBDR.F344-(D4Rat102-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRatlymphopenia  IAGP compared to BBDR.F344-(D4Rat153-D4Rhw8) and BBDP-(D4Rhw6-D4Rat62)/RhwRGD 
BBDR.F344-(D4Rat102-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/1RhwRatlymphopenia  IAGP compared to BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRGD 
BBDR.F344-(D4Rat102-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/2RhwRatlymphopenia  IAGP  RGD 
BBDR.F344-(D4Rat102-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/3RhwRatlymphopenia  IAGP compared to BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRGD 
BBDR.F344-(D4Rat153-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRatlymphopenia  IAGP compared to BBDR.F344-(D4Rat153-D4Rhw8) and BBDP-(D4Rhw6-D4Rat62)/RhwRGD 
BBDR.F344-(D4Rat153-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatlymphopenia  IAGP compared to BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRGD 
BBDR.F344-(D4Rat253-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRatlymphopenia  IAGP compared to BBDR.F344-(D4Rat153-D4Rhw8) and BBDP-(D4Rhw6-D4Rat62)/RhwRGD 
BBDR.F344-(D4Rat253-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatlymphopenia  IAGP compared to BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRGD 
BBDR.F344-(D4Rat26-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatlymphopenia  IAGP  RGD 
BBDR.F344-(D4Rat27-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatlymphopenia  IAGP compared to BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRGD 
BBDP/RhwRattype 1 diabetes mellitus MODEL: spontaneousIAGP  RGD 
BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRattype 1 diabetes mellitus susceptibilityIAGP compared to BBDR/RhwRGD 
BBDR.F344-(D4Arb11-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRattype 1 diabetes mellitus penetranceIAGP compared to BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRGD 
BBDR.F344-(D4Got59-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRattype 1 diabetes mellitus penetranceIAGP compared to BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRGD 
BBDR.F344-(D4Rat102-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRattype 1 diabetes mellitus penetranceIAGP compared to BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRGD 
BBDR.F344-(D4Rat102-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/3RhwRattype 1 diabetes mellitus susceptibilityIAGP compared to BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRGD 
BBDR.F344-(D4Rat153-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRattype 1 diabetes mellitus penetranceIAGP compared to BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRGD 
BBDR.F344-(D4Rat253-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRattype 1 diabetes mellitus penetranceIAGP compared to BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRGD 
BBDR.F344-(D4Rat26-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRattype 1 diabetes mellitus penetranceIAGP compared to BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRGD 
BBDR.F344-(D4Rat27-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRattype 1 diabetes mellitus penetranceIAGP compared to BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRGD 
Iddm38Rattype 1 diabetes mellitus resistanceIDA  RGD 
Iddm39Rattype 1 diabetes mellitus resistanceIDA  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BBDR.F344-(D4Rat253-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatdecreased lymphocyte cell number  IAGP  RGD 
BBDR.F344-(D4Arb11-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRatdecreased susceptibility to autoimmune diabetes  IAGP compared to BBDR.BBDP-D4Rhw11-D4Rhw10/RhwRGD 
BBDR.F344-(D4Got33-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatdecreased susceptibility to autoimmune diabetes  IAGP  RGD 
BBDR.F344-(D4Got59-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatdecreased susceptibility to autoimmune diabetes  IAGP as compared to BBDR.BBDP-D4Rhw11-D4Rhw10/RhwRGD 
BBDR.F344-(D4Rat102-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRatdecreased susceptibility to autoimmune diabetes  IAGP as compared to BBDR.BBDP-D4Rhw11-D4Rhw10/RhwRGD 
BBDR.F344-(D4Rat102-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/1RhwRatdecreased susceptibility to autoimmune diabetes  IAGP  RGD 
BBDR.F344-(D4Rat102-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/2RhwRatdecreased susceptibility to autoimmune diabetes  IAGP  RGD 
BBDR.F344-(D4Rat102-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/3RhwRatdecreased susceptibility to autoimmune diabetes  IAGP as compared to BBDR.BBDP-D4Rhw11-D4Rhw10/RhwRGD 
BBDR.F344-(D4Rat153-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRatdecreased susceptibility to autoimmune diabetes  IAGP as compared to BBDR.BBDP-D4Rhw11-D4Rhw10/RhwRGD 
BBDR.F344-(D4Rat153-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatdecreased susceptibility to autoimmune diabetes  IAGP compared to BBDR.BBDP-D4Rhw11-D4Rhw10/RhwRGD 
BBDR.F344-(D4Rat253-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRatdecreased susceptibility to autoimmune diabetes  IAGP as compared to BBDR.BBDP-D4Rhw11-D4Rhw10/RhwRGD 
BBDR.F344-(D4Rat253-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatdecreased susceptibility to autoimmune diabetes  IAGP  RGD 
BBDR.F344-(D4Rat26-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatdecreased susceptibility to autoimmune diabetes  IAGP  RGD 
BBDR.F344-(D4Rat27-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatdecreased susceptibility to autoimmune diabetes  IAGP as compared to BBDR.BBDP-D4Rhw11-D4Rhw10/RhwRGD 
BBDR/RhwRatdecreased susceptibility to autoimmune diabetes  IAGP compared to BBDR.BBDP-D4Rhw11-D4Rhw10/RhwRGD 
Iddm38Ratdecreased susceptibility to autoimmune diabetes  IDA  RGD 
Iddm39Ratdecreased susceptibility to autoimmune diabetes  IDA  RGD 
BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRatdecreased T cell number  IAGP compared to BBDR/RhwRGD 
BBDR.F344-(D4Arb11-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRatdecreased T cell number  IAGP  RGD 
BBDR.F344-(D4Got33-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatdecreased T cell number  IAGP  RGD 
BBDR.F344-(D4Got59-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatdecreased T cell number  IAGP  RGD 
BBDR.F344-(D4Rat102-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRatdecreased T cell number  IAGP  RGD 
BBDR.F344-(D4Rat102-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/1RhwRatdecreased T cell number  IAGP  RGD 
BBDR.F344-(D4Rat102-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/2RhwRatdecreased T cell number  IAGP  RGD 
BBDR.F344-(D4Rat102-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/3RhwRatdecreased T cell number  IAGP  RGD 
BBDR.F344-(D4Rat153-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRatdecreased T cell number  IAGP  RGD 
BBDR.F344-(D4Rat153-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatdecreased T cell number  IAGP compared to BBDR.BBDP-D4Rhw11-D4Rhw10/RhwRGD 
BBDR.F344-(D4Rat253-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRatdecreased T cell number  IAGP  RGD 
BBDR.F344-(D4Rat26-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatdecreased T cell number  IAGP  RGD 
BBDR.F344-(D4Rat27-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatdecreased T cell number  IAGP  RGD 
BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRatincreased susceptibility to autoimmune diabetes  IAGP compared to BBDR/RhwRGD 
BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRatinsulitis susceptibilityIAGP  RGD 
Iddm38Ratinsulitis resistanceIDA  RGD 
Iddm39Ratinsulitis resistanceIDA  RGD 
BBDR.BBDP-(D4Rhw11-D4Rhw10)/RhwRatperiinsulitis susceptibilityIAGP  RGD 
BBDR.F344-(D4Arb11-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRatperiinsulitis susceptibilityIAGP  RGD 
BBDR.F344-(D4Got33-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatperiinsulitis susceptibilityIAGP  RGD 
BBDR.F344-(D4Got59-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatperiinsulitis susceptibilityIAGP  RGD 
BBDR.F344-(D4Rat102-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRatperiinsulitis susceptibilityIAGP  RGD 
BBDR.F344-(D4Rat102-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/1RhwRatperiinsulitis susceptibilityIAGP  RGD 
BBDR.F344-(D4Rat102-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/2RhwRatperiinsulitis susceptibilityIAGP  RGD 
BBDR.F344-(D4Rat102-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/3RhwRatperiinsulitis susceptibilityIAGP  RGD 
BBDR.F344-(D4Rat153-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRatperiinsulitis susceptibilityIAGP  RGD 
BBDR.F344-(D4Rat153-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatperiinsulitis susceptibilityIAGP  RGD 
BBDR.F344-(D4Rat253-D4Rat27),BBDP-(D4Rhw11-D4Rhw10)/RhwRatperiinsulitis susceptibilityIAGP  RGD 
BBDR.F344-(D4Rat253-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatperiinsulitis susceptibilityIAGP  RGD 
BBDR.F344-(D4Rat26-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatperiinsulitis susceptibilityIAGP  RGD 
BBDR.F344-(D4Rat27-D4Rhw8),BBDP-(D4Rhw6-D4Rat62)/RhwRatperiinsulitis susceptibilityIAGP  RGD 
BBDR.F344-(D4Mgh24-D4Rhw6),BBDP-(D4Rhw6-D4Rhw10)/RhwRatperiinsulitis susceptibilityIAGP  RGD 


Additional Information