RGD Reference Report - A functional polymorphism of Ptpn22 is associated with type 1 diabetes in the BioBreeding rat. - Rat Genome Database

Send us a Message



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

A functional polymorphism of Ptpn22 is associated with type 1 diabetes in the BioBreeding rat.

Authors: Sarmiento, J  Wallis, RH  Ning, T  Marandi, L  Chao, G  Veillette, A  Lernmark, A  Paterson, AD  Poussier, P 
Citation: Sarmiento J, etal., J Immunol. 2015 Jan 15;194(2):615-29. doi: 10.4049/jimmunol.1302689. Epub 2014 Dec 12.
RGD ID: 9835029
Pubmed: PMID:25505293   (View Abstract at PubMed)
DOI: DOI:10.4049/jimmunol.1302689   (Journal Full-text)

The R620W variant of PTPN22 is one of the major genetic risk factors for several autoimmune disorders including type 1 diabetes (T1D) in humans. In the BioBreeding T1D-prone (BBDP) rat, a single nucleotide polymorphism in Ptpn22 results in an A629T substitution immediately C-terminal to the aliphatic residues central to the Ptpn22-C-terminal Src kinase interaction. This variant exhibits a 50% decrease in C-terminal Src kinase binding affinity and contributes to T cell hyperresponsiveness. Examination of BBDP sublines congenic for the Iddm26.2 locus that includes Ptpn22 has not only shown an expansion of activated CD4(+)25(+) T lymphocytes in animals homozygous for the BBDP allele, consistent with enhanced TCR-mediated signaling, but also a decrease in their proportion of peripheral Foxp3(+) regulatory T cells. Furthermore, clinical assessment of both an F2(BBDP x ACI.1u.Lyp) cohort and Iddm26.2 congenic BBDP sublines has revealed an association of Ptpn22 with T1D. Specifically, in both cases, T1D risk is significantly greater in BBDP Ptpn22 homozygous and heterozygous animals. These findings are consistent with a role for rat Ptpn22 allelic variation within Iddm26.2 in the regulation of T cell responses, and subsequently the risk for development of T1D.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTPN22Humantype 1 diabetes mellitus susceptibilityISOPtpn22 (Rattus norvegicus)DNA:missense mutation:cds:p.A629T (rat)RGD 
Ptpn22Rattype 1 diabetes mellitus susceptibilityIAGP DNA:missense mutation:cds:p.A629T (rat)RGD 
Ptpn22Mousetype 1 diabetes mellitus susceptibilityISOPtpn22 (Rattus norvegicus)DNA:missense mutation:cds:p.A629T (rat)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ptpn22Ratregulation of calcium ion transmembrane transport  IMP  RGD 
Ptpn22Ratregulation of peptidyl-tyrosine phosphorylation  IMP  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CskRatprotein phosphatase binding  IPIPtpn22 (Rattus norvegicus) RGD 
Ptpn22Ratprotein tyrosine kinase binding  IPICsk (Rattus norvegicus) RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ptpn22Rathyperglycemia  IAGP  RGD 
Ptpn22Ratincreased urine glucose level  IAGP  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Csk  (C-terminal Src kinase)
Ptpn22  (protein tyrosine phosphatase, non-receptor type 22)

Genes (Mus musculus)
Ptpn22  (protein tyrosine phosphatase, non-receptor type 22 (lymphoid))

Genes (Homo sapiens)
PTPN22  (protein tyrosine phosphatase non-receptor type 22)

Objects referenced in this article
Strain ACI.BBDP-(RT1u)(Gimap5)/Sunn null Rattus norvegicus
Strain BBDP/WorSunn null Rattus norvegicus

Additional Information