Prevention of Murine Erythropoietic Protoporphyria-Associated Skin Photosensitivity and Liver Disease by Dermal and Hepatic Ferrochelatase  Robert Pawliuk,

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Prevention of Murine Erythropoietic Protoporphyria-Associated Skin Photosensitivity and Liver Disease by Dermal and Hepatic Ferrochelatase  Robert Pawliuk, Robert Tighe, Robert J. Wise, Micheline M. Mathews-Roth, Philippe Leboulch  Journal of Investigative Dermatology  Volume 124, Issue 1, Pages 256-262 (January 2005) DOI: 10.1111/j.0022-202X.2004.23529.x Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Concentration of erythrocytic protoporphyrin (A) and percentage of protoporphyrin fluorescent red blood cells (B) 3 mo post-transplantation. BALB/C recipient mice were transplanted with either disease erythropoietic protoporphyria (EPP) marrow (EPP-BALB/C) (five mice) or normal marrow (BALB/C–BALB/C) (three mice). Two non-transplanted (Non-Tx) BALB/C and two EPP mice were used as controls. Journal of Investigative Dermatology 2005 124, 256-262DOI: (10.1111/j.0022-202X.2004.23529.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Fluorescent activated cell sorting analysis of red blood cells for protoporphyrin specific fluorescence 3 mo post-transplantation. Non-transplanted (Non-Tx) BALB/C and erythropoietic protoporphyria (EPP) mice were used as controls. The percentage of protoporphyrin fluorescent red blood cells is shown. BM, bone marrow. Journal of Investigative Dermatology 2005 124, 256-262DOI: (10.1111/j.0022-202X.2004.23529.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Lack of liver disease in BALB/C recipients of erythropoietic protoporphyria (EPP) marrow. One representative BALB/C recipient of BALB/C or EPP marrow was sacrificed 3 mo post-transplantation and the livers processed for histopathology. Sections were stained with hematoxylin/eosin and analyzed by a Board Certified Veterinary Pathologist. Sections analyzed at × 20 magnification (left panels) show the presence of large regenerative nodules (arrow) in the non-transplanted (Non-Tx) EPP mouse but not in livers of BALB/C recipients of either BALB/C or EPP marrow. Tissue sections analyzed at × 100 magnification (right panels) showed biliary cirrhosis, large vacuoles, and extracellular protoporphyrin deposits in the liver of the non-transplanted EPP mouse whereas no abnormalities were observed in the livers of BALB/C recipients of either BALB/CV or EPP marrow. BM, bone marrow. Journal of Investigative Dermatology 2005 124, 256-262DOI: (10.1111/j.0022-202X.2004.23529.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 BALB/C recipients of erythropoietic protoporphyria (EPP) marrow show only very mild photosensitivity despite greatly elevated levels of circulating protoporphyrin. At 3 mo post-transplantation mice were shaved, depilated, and exposed to a mercury vapor lamp (5.52 J per cm2 of 400–410 nm light) to mimic exposure to sunlight. Photographs were taken 5 d post-exposure. Non-transplanted (Non-Tx) normal BALB/C (A) and EPP (B) mice were used as controls. The bottom panels show two BALB/C recipients transplanted with EPP marrow (C, D). Note the very mild photosensitivity (small areas of mild ulceration) as compared with the non-transplanted EPP mouse (large areas of severe ulceration and crusting). Journal of Investigative Dermatology 2005 124, 256-262DOI: (10.1111/j.0022-202X.2004.23529.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Normal levels of ferrochelatase expressed in the skin protects against photosensitivity. One month following skin transplantation the backs of mice were shaved, depilated, and exposed to 20 min of a mercury vapor lamp. Areas of the skin graft are circled. The erythropoietic protoporphyria (EPP) recipient of the BALB/C skin graft shows burns over a large area of the back. Note the lack of burns within the area of the normal skin graft. Journal of Investigative Dermatology 2005 124, 256-262DOI: (10.1111/j.0022-202X.2004.23529.x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions