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Induction of Skin Fibrosis in Mice Expressing a Mutated Fibrillin-1 Gene

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Abstract

Background

Tight skin mice (TSK) bear a mutated Fibrillin-1 (Fbn-1) gene. Genetic studies show that the TSK mutation is closely associated with the Fbn-1 locus (0–0.7 cM). A previous study showed two recombinants between the Fbn-1 locus and the TSK mutation. TSK mutation and mutated Fbn-1 gene cosegregate in F1 mice.

Materials and Methods

To elucidate the role of the mutated Fbn-1 gene in occurrence of TSK syndrome, we generated transgenic (Tg) mice expressing mutated Fbn-1 gene. In another set of experiments, we injected normal mice after birth with a plasmid bearing mutated Fbn-1 gene (pdFbn-1).

Results

Our results demonstrate that the pdFbn-1 Tg mice developed permanent cutaneous hyperplasia that was permanent. In mice injected as newborns with a plasmid bearing the sense pdFbn-1 gene, cutaneous hyperplasia was transient. In contrast to TSK mice, neither Tg nor mice injected with plasmid developed lung emphysema. The pdFbn-1 Tg and TSK mice spontaneously produced anti-topoisomerase I and anti-Fbn-1 antibodies, as do humans afflicted by scleroderma; whereas, those injected with a plasmid containing the pdFbn-1 gene produced only anti-Fbn-1 autoantibodies.

Conclusions

The results suggest that, although cutaneous hyperplasia is due to mutated Fbn-1 gene, the TSK syndrome may be multifactorial.

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Acknowledgment

This study was supported by grants from the Scleroderma Foundation and NIH-NIAID PO1 AI 2467–11 and by the C.O.E.grant from the Ministry of Education, Science, Sport and Culture of Japan.

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Authors and Affiliations

  1. Department of Microbiology, Mount Sinai School of Medicine, Annenberg Bld. 16–60, One Gustave Levy Place, Box1124, New York, New York, 10029, USA

    Shinichiro Saito &  Constantin Bona

  2. Department of Pathology, Mount Sinai School of Medicine, New York, USA

    Robert G. Phelps

  3. Department of Biochemistry, Mount Sinai School of Medicine, New York, USA

    Imre Wolf

  4. Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Hiroyuki Nishimura & Tasuku Honjo

  5. Center for Animal Resources, Kumamoto University, Kumamoto, Japan

    Mihsa Suzuki

Authors
  1. Shinichiro Saito
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  2. Hiroyuki Nishimura
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  3. Robert G. Phelps
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  4. Imre Wolf
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  5. Mihsa Suzuki
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  6. Tasuku Honjo
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  7. Constantin Bona
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Corresponding author

Correspondence to Constantin Bona.

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Saito, S., Nishimura, H., Phelps, R.G. et al. Induction of Skin Fibrosis in Mice Expressing a Mutated Fibrillin-1 Gene. Mol Med 6, 825–836 (2000). https://doi.org/10.1007/BF03401821

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  • DOI: https://doi.org/10.1007/BF03401821

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