Induction of skin fibrosis in mice expressing a mutated fibrillin-1 gene.

S. Saito, H. Nishimura, R. G. Phelps, I. Wolf, M. Suzuki, T. Honjo, C. Bona

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31 Citations (Scopus)


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- 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.

Original languageEnglish
Pages (from-to)825-836
Number of pages12
JournalMolecular medicine (Cambridge, Mass.)
Issue number10
Publication statusPublished - 2000 Oct
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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