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See detailEuroPhenome: a repository for high-throughput mouse phenotyping data
Morgan, Hugh; Beck, Tim; Blake, Andrew et al

in Nucleic Acids Research (2010), 38(1), 577-585

The broad aim of biomedical science in the postgenomic era is to link genomic and phenotype information to allow deeper understanding of the processes leading from genomic changes to altered phenotype and ... [more ▼]

The broad aim of biomedical science in the postgenomic era is to link genomic and phenotype information to allow deeper understanding of the processes leading from genomic changes to altered phenotype and disease. The EuroPhenome project (http://www.EuroPhenome.org) is a comprehensive resource for raw and annotated highthroughput phenotyping data arising from projects such as EUMODIC. EUMODIC is gathering data from the EMPReSSslim pipeline (http://www.empress .har.mrc.ac.uk/) which is performed on inbred mouse strains and knock-out lines arising from the EUCOMM project. The EuroPhenome interface allows the user to access the data via the phenotype or genotype. It also allows the user to access the data in a variety of ways, including graphical display, statistical analysis and access to the raw data via web services. The raw phenotyping data captured in EuroPhenome is annotated by an annotation pipeline which automatically identifies statistically different mutants from the appropriate baseline and assigns ontology terms for that specific test. Mutant phenotypes can be quickly identified using two EuroPhenome tools: PhenoMap, a graphical representation of statistically relevant phenotypes, and mining for a mutant using ontology terms. To assist with data definition and cross-database comparisons, phenotype data is annotated using combinations of terms from biological ontologies. [less ▲]

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See detailReduced intragraft mRNA expression of matrix metalloproteinases Mmp3, Mmp12, Mmp13 and Adam8, and diminished transplant arteriosclerosis in Ccr5-deficient mice.
Luckow, Bruno; Joergensen, Joanne; Chilla, Silvia et al

in European Journal of Immunology (2004), 34(9), 2568-78

Experimental and human organ transplant studies suggest an important role for chemokine (C-C-motif) receptor-5 (CCR5) in the development of acute and chronic allograft rejection. Because early transplant ... [more ▼]

Experimental and human organ transplant studies suggest an important role for chemokine (C-C-motif) receptor-5 (CCR5) in the development of acute and chronic allograft rejection. Because early transplant damage can predispose allografts to chronic dysfunction, we sought to identify potential pathophysiologic mechanisms leading to allograft damage by using wild-type and Ccr5-deficient mice as recipients of fully MHC-mismatched heart and carotid-artery allografts. Gene expression in rejecting heart allografts was analyzed 2 and 6 days after transplantation using Affymetrix GeneChips. Microarray analysis led to identification of four metalloproteinase genes [matrix metalloproteinase (Mmp)3, Mmp12, Mmp13 and a disintegrin and metalloprotease domain (Adam)8] with significantly diminished intragraft mRNA expression in Ccr5-deficient mice at day 6. Accordingly, allografts from Ccr5-deficient mice showed less tissue remodeling and hence better preservation of the myocardial architecture compared with allografts from wild-type recipients. Moreover, survival of cardiac allografts was significantly increased in Ccr5-deficient mice. Carotid artery allografts from Ccr5-deficient recipients showed better tissue preservation, and significant reduction of neointima formation and CD3+ T cell infiltration. Ccr5 appears to play an important role in transplant-associated arteriosclerosis that may involve metalloproteinase-mediated vessel wall remodeling. We conclude that early tissue remodeling may be a critical feature in the predisposition of allografts to the development of chronic dysfunction. [less ▲]

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