Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes.
Mice deficient in programmed cell death 1 (PD-1, Pdcd1), an immunoinhibitory receptor belonging to the CD28/cytotoxic T lymphocyte-associated antigen-4 family, spontaneously develop lupus-like autoimmune disease and autoimmune dilated cardiomyopathy on C57BL/6 and BALB/c backgrounds, respectively. However, how PD-1 deficiency induces different forms of autoimmune diseases on these two strains was unknown. Here, we report that PD-1 deficiency specifically accelerates the onset and frequency of type I diabetes in NOD (nonobese diabetic) mice, with strong T helper 1 polarization of T cells infiltrating into islets. These results suggest that PD-1 deficiency accelerates autoimmune predisposition of the background strain, leading to the induction of different forms of autoimmune diseases depending on the genetic background of the strain. Using NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes, we screened diabetes-susceptible loci by genetic linkage analysis. The diabetic incidence of NOD-Pdcd1-/- mice was controlled by five genetic loci, including three known recessive loci [ Idd (insulin-dependent diabetes) 1, Idd17, and Idd20] and two previously unidentified dominant loci [ Iddp ( Idd under PD-1 deficiency) 1 and Iddp2].[1]References
- Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes. Wang, J., Yoshida, T., Nakaki, F., Hiai, H., Okazaki, T., Honjo, T. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
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