Dataset Information

Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes.

ABSTRACT: 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].

SUBMITTER: Wang J

PROVIDER: S-EPMC1188011 | biostudies-literature | 2005 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes.

Wang Jian J Yoshida Taku T Nakaki Fumio F Hiai Hiroshi H Okazaki Taku T Honjo Tasuku T

Proceedings of the National Academy of Sciences of the United States of America 20050808 33

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 ty ...[more]

PMID: 16087865

Similar Datasets

Project description:We used high density oligonucleotide arrays to measure the relative expression levels of >39,000 genes and ESTs in the NOD mouse (a murine model of T1D and other autoimmune conditions), four NOD-derived diabetes resistant congenic strains and two nondiabetic control strains. Owing to the importance of T cells in the development of T1D we decided to target two organs, the spleen and thymus. We profiled gene expression in thymi from four week old female mice and spleens from three month old female mice. For each of the 14 strain-tissue combinations (7 strains x 2 tissues) we performed two independent replicate experiments, making the total number of hybridizations performed 28. In each case, an RNA population from a pool of two or three organs was generated to minimize the chances of within strain variation masking genuine variation between the strains. To minimize any variation introduced during target preparation, all samples within a given replicate group were processed in parallel. Three samples from group two (spleen: B10.H2g7_S2 http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gsm594 (GSM594); thymus: B10.H2g7_T2 http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gsm608 (GSM608), B10.H2g7 Idd3_T2 http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gsm609 (GSM609)) and one from group one (spleen B10.H2g7_S1 http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gsm587 (GSM587) failed a preliminary quality control check. Consequently, the steps involved in preparing labelled cRNA from the initial starting material had to be repeated for these four samples at a later date. A subsequent comparison of the variation seen between samples within the same replicate group (samples processed in parallel) versus samples in distinct replicate groups (samples processed at different times) revealed that the variation between the two groups (i.e. owing to independent sample preparation) was higher than the small amount of variation between the closely matched strains. Ignoring the variability introduced during sample preparation was therefore likely to result in spurious changes being detected and genuine strain-specific differences in gene expression being masked. Consequently, we decided to exclude the four samples that had had to be prepared independently owing to failing initial quality control. Keywords = NOD, diabetes, congenic Keywords: other

Dataset Information

Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes.

Publications

Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets