| First Author | Sawalha AH | Year | 2007 |
| Journal | Eur J Immunol | Volume | 37 |
| Issue | 5 | Pages | 1407-13 |
| PubMed ID | 17429846 | Mgi Jnum | J:123548 |
| Mgi Id | MGI:3718816 | Doi | 10.1002/eji.200636872 |
| Citation | Sawalha AH, et al. (2007) Defective DNA methylation and CD70 overexpression in CD4+ T cells in MRL/lpr lupus-prone mice. Eur J Immunol 37(5):1407-13 |
| abstractText | We have determined that abnormal DNA methylation in T cells coincides with the development of autoimmunity, using a mouse model that exhibits an age-dependent lupus-like disease (MRL/lpr mice). Splenic CD4(+) T cells were isolated from these mice at 5 and 16 wk of age (before and after autoimmunity is established) and the expression of DNA methyltransferase 1 (Dnmt1) and the methylation-sensitive gene Tnfsf7 (CD70) was measured. Bisulfite DNA sequencing was used to monitor the methylation status of the Tnfsf7 gene. We found that Dnmt1 steady-state mRNA levels were significantly lower in 16-wk-old MRL/lpr mice, which had established autoimmunity, compared to the 5-wk-old MRL/lpr mice. Furthermore, the expression of CD70 was higher in MRL/lpr mice at 16 wk. CD70 was overexpressed in MRL/lpr mice compared to age- and sex-matched MRL(+/+) controls. Bisulfite DNA sequencing of the Tnfsf7 gene in MRL/lpr mice revealed that at 16 wk, CG pairs were hypomethylated compared to 5-wk-old mice, and that Tnfsf7 from MRL/lpr mice was hypomethylated at 16 wk relative to age-matched MRL(+/+) controls. Our data indicate that decreased expression of Dnmt1 and the corresponding T cell DNA hypomethylation correlate with the development of age-dependent autoimmunity in MRL/lpr mice. |
