title: Generation of a new congenic mouse strain with enhanced chymase expression in mast cells.
abstract: Mast cells are effector cells best known for their roles in IgE-associated allergy, but they also play a protective role in defense against pathogens. These cells express high levels of proteases including chymase, tryptase and carboxypeptidase. In the present study, we identified a congenic strain of C57BL/6 mice expressing an extraordinarily high level of chymases Mcp-2 and Mcp-4 in mast cells. The overexpression was associated with variant Mcp-2 and Mcp-4 genes originated from DBA/2 mice that also expressed high levels of the two enzymes. Real time PCR analysis revealed that Mcp-2 and Mcp-4 were selectively overexpressed as tryptases, Cpa3 and several other chymases were kept at normal levels. Reporter gene assays demonstrated that single-nucleotide polymorphisms (SNPs) in the promoter region of Mcp-2 gene may be partly responsible for the increased gene transcription. Our study provides a new model system to study the function of mast cell chymases. The data also suggest that expression of chymases differs considerably in different strains of mice and the increased chymase activity may be responsible for some unique phenotypes observed in DBA/2 mice.
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Xi
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Wanke
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America ; Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun, China.
authors.forename: Kaiyao
authors.initials: K
authors.lastname: Shi
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Wanting T
authors.initials: WT
authors.lastname: Ho
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Zhizhuang J
authors.initials: ZJ
authors.lastname: Zhao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D053818:Chymases / Q000378:metabolism*; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D005455:Fluorescent Antibody Technique; D008407:Mast Cells / Q000201:enzymology*; D051379:Mice; D020297:Mice, Congenic / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D040901:Proteomics; D060888:Real-Time Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000378:metabolism
chemical_list: D017931:DNA Primers; D012697:Serine Endopeptidases; C083294:chymase 2; C066932:mast cell protease 4; D053818:Chymases