التفاصيل البيبلوغرافية
| العنوان: |
Amino acid polymorphisms altering the glycosylation of IL-2 do not protect from type 1 diabetes in the NOD mouse. |
| المؤلفون: |
Kamanaka, Masahito, Rainbow, Dan, Schuster-Gossler, Karin, Eynon, Elizabeth E., Chervonsky, Alexander V., Wicker, Linda S., Flavell, Richard A. |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 7/7/2009, Vol. 106 Issue 27, p11236-11240, 5p |
| مصطلحات موضوعية: |
DIABETES, AMINO acids, GENETIC polymorphisms, GLYCOSYLATION, LABORATORY mice |
| مستخلص: |
Idd3 is one of many gene regions that affect the development of type 1 diabetes (T1D) in the nonobese diabetic (NOD) mouse. Idd3 has been localized to a 650-kb region on chromosome 3 containing the IL-2 gene. Exon 1 of the IL-2 gene is polymorphic between the susceptible NOD and the protective C57BL/6 (B6) alleles, causing multiple amino acid changes that have been proposed to be responsible for the differing glycosylation status. To address whether this coding polymorphism recapitulates the disease suppression mediated by the 86 Idd3 allele, we generated knockin mice in which exon 1 of the B6 lL-2 allele replaces the homologous region in the NOD allele. We generated these mice by targeting the NOD allele of NOD/129 F1 ES cells. lL-2 protein from the knockin mice showed the glycosylation pattern of the B6 IL-2 isoform, confirming that the amino acid differences encoded within exon 1 affect the glycosylation of the IL-2 protein. However, unlike NOD.B6 Idd3 congenic mice, the knockin mice were not protected from Ti D. Furthermore, the difference in amino acid sequence in the lL-2 protein did not affect the level of expression of lL-2. This approach provides a general method for the determination of a functional role of a given genomic sequence in a disease process. Further, our result demonstrates that the variants in exon 1 of the IL-2 gene are not responsible for T1D suppression in NOD.B6 Idd3 mice, thereby supporting the hypothesis that variants in the regulatory region affecting expression levels are causative. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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