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

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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.



Disease Annotations    

Gene Ontology Annotations    

Biological Process

Molecular Function

Phenotype Annotations    

Mammalian Phenotype
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