title: Protein-tyrosine phosphatase sigma is associated with ulcerative colitis.
abstract: Inflammatory bowel disease (IBD), a relatively common chronic debilitating intestinal illness, is composed of two broadly defined groups, Crohn's disease (CD) and ulcerative colitis (UC). Although several susceptibility genes for CD have been recently described, susceptibility genes exclusive for UC have not been forthcoming. Here, we show that receptor protein-tyrosine phosphatase sigma (PTPRS-encoding PTPsigma) knockout mice spontaneously develop mild colitis that becomes severe when challenged with two known inducers of colitis. We also demonstrate that E-cadherin and beta-catenin, two important adherens junction proteins involved in maintenance of barrier defense in the colon, act as colonic substrates for PTPsigma. Furthermore, we show that three SNPs (rs886936, rs17130, and rs8100586) that flank exon 8 in the human PTPRS gene are associated with UC. The presence of these SNPs is associated with novel splicing that removes the third immunoglobulin-like domain (exon 9) from the extracellular portion of PTPsigma, possibly altering dimerization or ligand recognition. We propose that polymorphisms in the human PTPRS gene lead to ulcerative colitis.
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, 555 University Ave, Toronto, Ontario, Canada.
authors.forename: Aleixo M
authors.initials: AM
authors.lastname: Muise
authors.forename: Thomas
authors.initials: T
authors.lastname: Walters
authors.forename: Eytan
authors.initials: E
authors.lastname: Wine
authors.forename: Anne M
authors.initials: AM
authors.lastname: Griffiths
authors.forename: Dan
authors.initials: D
authors.lastname: Turner
authors.forename: Richard H
authors.initials: RH
authors.lastname: Duerr
authors.forename: Miguel D
authors.initials: MD
authors.lastname: Regueiro
authors.forename: Bo-Yee
authors.initials: BY
authors.lastname: Ngan
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Philip M
authors.initials: PM
authors.lastname: Sherman
authors.forename: Mark S
authors.initials: MS
authors.lastname: Silverberg
authors.forename: Daniela
authors.initials: D
authors.lastname: Rotin
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000201:enzymology* / Q000378:metabolism; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020641:Polymorphism, Single Nucleotide; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015820:Cadherins; D051176:beta Catenin; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2