Expression, Genomic Structure and Mapping of the Thymus Specific Protease Prss16: A Candidate Gene for Insulin Dependent Diabetes Mellitus Susceptibility

• Published in: Journal of autoimmunity 2002-06, Vol.18 (4), p.311-316
• Main Authors: Cheunsuk, Saijai, Sparks, Rachel, Noveroske, Janice K., Hsu, Tom, Justice, Monica J., Gershwin, M.Eric, Gruen, Jeffrey R., Bowlus, Christopher L.
• Format: Article
• Language: English
• Subjects: Animals; autoimmunity, gene expression, Prss16, thymus; Base Sequence; Biological and medical sciences; Chromosome Mapping; Diabetes Mellitus, Type 1 - etiology; Diabetes Mellitus, Type 1 - genetics; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Genetic Predisposition to Disease; Humans; In Situ Hybridization; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, Inbred NZB; Molecular Sequence Data; Sequence Analysis, DNA; Serine Endopeptidases - biosynthesis; Serine Endopeptidases - genetics
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1006/jaut.2002.0593

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.