Animal model of sclerotic skin. III: Histopathological comparison of bleomycin-induced scleroderma in various mice strains.
We have recently established a mouse model for scleroderma by repeated local bleomycin treatment. In this study, we compared the susceptibility to bleomycin in the development of dermal sclerosis among Balb/c, C3H/He, C57BL/6J, A/J, DBA/2, B10.BR, B10.A, and B10.D2 mouse strains. After either bleomycin or PBS treatment, skin from the injection site was histologically examined. Dermal sclerosis was induced by bleomycin treatment for 4 weeks in all of the strains examined. In particular, C3H/He, DBA/2, B10.D2 and B10.A mice developed intense dermal sclerosis characterized by deposition of homogeneous material in the dermis and thickened collagen bundles. Dermal thickness showed a more than twofold increase following bleomycin treatment, as compared with PBS treatment, except in C57BL/6J and DBA/2 mice. In A/J, C3H/He, B10.A, and B10.D2 mice, dermal thickness showed a more than 2.5-fold increase. Mast cell numbers in sclerotic skin were significantly greater than in PBS-treated skin in Balb/c and B10.A mice after 4 weeks of treatment. We also examined whether bleomycin treatment for 3 weeks could induce dermal sclerosis in C3H mice. Histological examination revealed that epidermal thickness as well as dermal sclerosis was increased in C3H mice following bleomycin treatment for 3 weeks. Increased hydroxyproline content as well as mRNA expression of alpha1(I) collagen, as determined by Northern blot analysis, were observed following bleomycin treatment. Taken together, we conclude that C3H/He and B10.A mouse strains are bleomycin-'susceptible', and these strains are considered to be a suitable experimental model of bleomycin-induced scleroderma.
Yamamoto
T
T
Department of Dermatology, Tokyo Medical and Dental University, School of Medicine, Japan. yamamoto.derm@med.tmd.ac.jp
Kuroda
M
M
Nishioka
K
K
D000818:Animals; D001761:Bleomycin / Q000009:adverse effects; D003094:Collagen / Q000235:genetics; D004195:Disease Models, Animal; D004817:Epidermis / Q000187:drug effects / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms
D012333:RNA, Messenger; D001761:Bleomycin; D003094:Collagen