Analysis of the IDDM Candidate Gene Prss16 in NOD and NON Mice

Abstract

The thymus-specific serine protease Prss16 is highly expressed by the epithelial cells in the thymic cortex. It has been suggested to play an important role in the positive selection of T cells through the antigen presention pathway of the cortical antigen presenting cells. Recently, the gene ecoding Prss16 has been linked to insulin dependent diabetes mellitus (IDDM) susceptibility independent of HLA-DR3 suggesting the Prss16 may be involved in the development of autoimmune disease. Due to the similarities of the gene structure and expression pattern between the human and mouse genes, we compared Prss16 between non-obese diabetic (NOD) and non-obese non-diabetic (NON) mice. Analysis of the Prss16 coding region failed to identify any differences in sequence. Northern analysis and semi-quantitative reverse transcriptase polymerase chain reaction showed that the mRNA was equal in size and abundance in the two strains. In situ hybridization showed similar patterns of staining. Therefore, our data suggests that there is no significant different in the gene structure, transcription level, and expression pattern of Prss16 gene between NOD and NON mice.

Thymus-specific serine protease controls autoreactive CD4 T cell development and autoimmune diabetes in mice

“…Published in situ hybridization studies showed that Tssp is predominantly expressed by cTECs but not to significant levels in the hematopoietic compartment (8,9,22). In agreement, we found very high levels of Prss16 mRNA in cTECs but not in medullary TECs.…”

“…Mice were immunized with the corresponding Ag in CFA, and their recall response was analyzed in vitro. Quite unexpectedly in light of the foremost role of insulin in diabetes development (31,32), we found that the frequency of IL-2-producing CD4 T cells specific for Ins [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] and Ins [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66] was comparable in Tssp° and WT NOD mice ( Figure 6). Likewise WT and Tssp° NOD mice responded similarly to the GAD 206-220 peptide and the known IGRP immunodominant epitopes ( Figure 6).…”

Thymus-specific serine protease contributes to the diversification of the functional endogenous CD4 T cell receptor repertoire

“…We next examined whether TSSP deficiency may likewise impact on the generation of a polyclonal HEL-specific CD4 T cell repertoire using BM chimeras. TSSP is highly expressed by cTEC (Bowlus et al, 1999;Carrier et al, 1999;Cheunsuk et al, 2002) but also, at lower levels, by thymic DCs (unpublished data). Therefore, we examined the effect of TSSP deficiency in radioresistant TECs on the differentiation of some HEL-specific CD4 T cells by injecting WT BM cells into lethally irradiated Tssp / NOD-C° mice (WT → KO) or, as control, into NOD-C° host (WT → WT).…”