{"doi":"10.1038/jid.2009.423","title":"Overexpression of Fetuin-A Counteracts Ectopic Mineralization in a Mouse Model of Pseudoxanthoma Elasticum (Abcc6−/−)","abstract":null,"journal":"Journal of Investigative Dermatology","year":2010,"id":681958,"datarank":0.5709993734655481,"base_score":3.8066624897703196,"endowment":3.8066624897703196,"self_citation_contribution":0.5709993734655481,"citation_network_contribution":0.0,"self_endowment_contribution":0.5709993734655481,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":44,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1781702,"name":"Florian Dibra","orcid":null,"position":1,"is_corresponding":false},{"id":556597,"name":"Michael D. Lee","orcid":null,"position":2,"is_corresponding":false},{"id":1434794,"name":"Reid Oldenburg","orcid":null,"position":3,"is_corresponding":false},{"id":207768,"name":"Jouni Uitto","orcid":null,"position":4,"is_corresponding":false},{"id":1779674,"name":"Qiujie Jiang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Overexpression of Fetuin-A Counteracts Ectopic Mineralization in a Mouse Model of Pseudoxanthoma Elasticum (Abcc6−/−)","abstract":"The pathologic hallmark of pseudoxanthoma elasticum (PXE) is ectopic mineralization of soft connective tissues. Recent studies have suggested that PXE is a metabolic disease, and perturbations in a number of circulatory factors have been postulated. One of them is fetuin-A, a 60-kDa glycoprotein synthesized in the liver and secreted into blood. Observations in targeted mutant mice (Ahsg(-/-)) and in cell culture model systems have shown that fetuin-A is a powerful anti-mineralization factor in circulation, and the serum levels of fetuin-A in patients with PXE as well as in a mouse model of PXE (Abcc6(-/-)) have been shown to be reduced by up to 30%. In this study, we tested the hypothesis that overexpression of fetuin-A in Abcc6(-/-) mice counteracts the ectopic mineralization. Delivery of an expression construct containing full-length mouse fetuin-A complementary DNA (cDNA), linked to a His-tag, to the liver of these mice resulted in elevated serum levels of this protein. As a consequence, soft tissue mineralization, which is a characteristic of Abcc6(-/-) mice, was reduced by approximately 70% at 12 weeks of age, but the effect was transient when examined 4 weeks later. The results suggest that normalization of serum fetuin-A, either through gene therapy approaches or by direct protein delivery to the circulation, may offer strategies for treating PXE and perhaps other heritable disorders of soft tissue mineralization.","is_dataset_classified":null,"base_score":3.8066624897703196,"endowment":3.8066624897703196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"20090764","pmcid":"PMC2891093","openalex_id":"https://openalex.org/W2002597388","authors":[],"funders":[{"funder_name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","grant_id":"R01AR28450","title":null},{"funder_name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","grant_id":"R01AR52627","title":null},{"funder_name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","grant_id":"R01AR55225","title":null},{"funder_name":"NIAMS NIH 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Non-Commercial","oa_locations":[{"url":"http://www.jidonline.org/article/S0022202X15347990/pdf","host_type":"journal"},{"url":"http://www.jidonline.org/article/S0022202X15347990/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0022202X15347990?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0022202X15347990?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1038/jid.2009.423","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/20090764","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2891093","host_type":"repository"},{"url":"https://escholarship.org/uc/item/0fk8d2x7","host_type":"repository"},{"url":"http://dx.doi.org/10.1038/jid.2009.423","host_type":""},{"url":"https://dx.doi.org/10.1038/jid.2009.423","host_type":""},{"url":"https://escholarship.org/content/qt0fk8d2x7/qt0fk8d2x7.pdf","host_type":""},{"url":"https://doi.org/https://doi.org/10.1038/jid.2009.423","host_type":""}],"fields_of_study":["Dermatological and Skeletal Disorders","Skin and Cellular Biology Research","Heterotopic Ossification and Related Conditions","0301 basic medicine","03 medical and health sciences","0303 health sciences","ATP-Binding Cassette Transporters","Animals","Blood Proteins","Calcinosis","Connective Tissue","Disease Models, Animal","Female","Gene Expression","Gene Transfer Techniques","Genetic Therapy","Lac Operon","Liver","Male","Mice","Mice, Mutant Strains","ATP-Binding Cassette, Sub-Family C Proteins","Pseudoxanthoma Elasticum","Transfection","Vibrissae","alpha-2-HS-Glycoprotein"],"mesh_terms":["Animals","Blood Proteins","Calcinosis","Connective Tissue","Disease Models, Animal","Female","Lac Operon","Liver","Male","Mice, Mutant Strains","Pseudoxanthoma Elasticum","Transfection","Vibrissae","Genetic Therapy","Gene Expression","Gene Transfer Techniques","ATP-Binding Cassette Transporters","Multidrug Resistance-Associated Proteins","ATP-Binding Cassette, Sub-Family C Proteins","Mice","alpha-2-HS-Glycoprotein"],"keywords":["Pseudoxanthoma elasticum","Fetuin","Ectopic calcification","Endocrinology","Internal medicine","Connective tissue","Mineralization (soil science)","Osteopontin","Glycoprotein","Biology","Pathology","Chemistry","Medicine","Calcification","Molecular biology","Male","ATP-Binding Cassette, Sub-Family C Proteins","alpha-2-HS-Glycoprotein","Medical Biotechnology","Clinical Sciences","Oncology and Carcinogenesis","Gene Expression","Dermatology","Transfection","Biochemistry","Mice","Rare Diseases","Genetics","2.1 Biological and endogenous factors","Animals","Biomedical and Clinical Sciences","Animal","Liver Disease","Dermatology & Venereal Diseases","Gene Transfer Techniques","Calcinosis","Cell Biology","Blood Proteins","Genetic Therapy","Stem Cell Research","Mice, Mutant Strains","Mutant Strains","Disease Models, Animal","Lac Operon","Liver","Vibrissae","Disease Models","Stem Cell Research - Nonembryonic - Non-Human","ATP-Binding Cassette Transporters","Female","Multidrug Resistance-Associated Proteins","Digestive Diseases","Biotechnology"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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