Prss16 is not required for T-cell development.

PRSS16 is a serine protease expressed exclusively in cortical thymic epithelial cells (cTEC) of the thymus, suggesting that it plays a role in the processing of peptide antigens during the positive selection of T cells. Moreover, the human PRSS16 gene is encoded in a region near the class I major histocompatibility complex (MHC) that has been linked to type 1 diabetes mellitus susceptibility. The mouse orthologue Prss16 is conserved in genetic structure, sequence, and pattern of expression. To study the role of Prss16 in thymic development, we generated a deletion mutant of Prss16 and characterized T-lymphocyte populations and MHC class II expression on cortical thymic epithelial cells. Prss16-deficient mice develop normally, are fertile, and show normal thymic morphology, cellularity, and anatomy. The total numbers and frequencies of thymocytes and splenic T-cell populations did not differ from those of wild-type controls. Surface expression of MHC class II on cTEC was also similar in homozygous mutant and wild-type animals, and invariant chain degradation was not impaired by deletion of Prss16. These findings suggest that Prss16 is not required for quantitatively normal T-cell development.

Expression, genomic structure and mapping of the thymus specific protease prss16: a candidate gene for insulin dependent diabetes mellitus susceptibility.

PRSS16 is a serine protease specifically expressed by epithelial cells in the thymic cortex. The human gene is encoded on 6p21.3-p22 where recent linkage analysis has identified an association with insulin dependent diabetes mellitus (IDDM) susceptibility independent of HLA-DR3. To further investigate its potential role in autoimmunity, we characterized the mouse orthologue, Prss16. The genomic structure of Prss16 shows conservation with the human gene in size, number of exons and chromosomal location. Mapping of Prss16 places it on mouse chromosome 13 centromeric of thesatin locus. This region is comparable to the PRSS16 region on human chromosome 6 and has also been linked to quantitative trait locus for IDDM in the nonobese diabetic mouse. Similar to the human gene, Prss16 expression is highly specific in the mouse with expression limited to the cortical thymic epithelium. Notably, embryonic expression coincides with population of the thymic anlage with T-cell precursors and initiation of T-cell development. We also show that NOD and New Zealand Black mice, which have a disrupted thymic architecture and autoimmune phenotype, have lower levels of Prss16 expression compared to C57BL/6 mice. These findings support the role of Prss16 in T-cell development and susceptibility to autoimmunity in the mouse.

Analysis of the IDDM candidate gene Prss16 in NOD and NON mice.

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 encoding 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.