Spotlight on Research 2010

December 2010 (historical)

Mouse Model Points to Potential Therapy for Skin Disease PXE

Scientists at Philadelphia’s Jefferson Medical College have found that restoring the normal blood concentration of an anti-mineralization protein in a mouse model of the skin disease pseudoxanthoma elasticum (PXE) reduces the abnormal deposit of minerals that characterizes the condition. The work, supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), suggests that the protein fetuin-A (a known anti-mineralization protein) could be a therapeutic target in PXE.

Scientists have thought that PXE, a rare inherited disorder of the body’s connective tissue, is caused by an imbalance between anti- and pro-mineralization processes mediated by factors in the blood. This, they say, leads to abnormal deposits of minerals which can lead to the loss of skin elasticity, impaired vision, and increased risk of cardiovascular disease. Jouni Uitto, M.D., Ph.D., Qiujie Jiang, M.D., Ph.D., and their colleagues at the Thomas Jefferson University’s Department of Dermatology and Cutaneous Biology and the Children’s Hospital of Philadelphia tested the hypothesis by surgically linking the blood circulation of a normal mouse to that of a mouse model of PXE. They found that the blood from the unaffected animal could reduce the abnormal mineralization in the PXE mouse, a discovery that supports the idea of an imbalance of blood-borne factors as a basic for the disease.

The scientists also looked at the blood concentration of the fetuin-A in PXE mice, and found it to be significantly lower than that of unaffected mice. By restoring the protein to its normal level, the research team reduced the effects of overmineralization. “Our observations suggest that reintroducing critical anti-mineralization factors into the blood circulation could be a way to attack this disorder,” says Dr. Uitto.

“Right now, there is no treatment for PXE,” says Dr. Uitto. “Our findings give us potential strategies to treat the disease and perhaps other heritable disorders of soft tissue mineralization.”

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The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services’ National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about the NIAMS, call the information clearinghouse at 301-495-4484 or 877-22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov.

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Jiang Q, et al. Parabiotic heterogenetic pairing of Abcc6-/-|Rag1-/- mice and their wild-type counterparts halts ectopic mineralization in a murine model of pseudoxanthoma elasticum. Am J Pathol 2010 176:1855-62, Epub 2010 Feb 25. PMID: 20185580. Jiang Q, et al. Overexpression of fetuin-A counteracts ectopic mineralization in a mouse model of pseudoxanthoma elasticum (Abcc6 -/-). J Invest Dermatol 2010 130:1288-96. Epub 2010 Jan 21. PMID: 20090764.