[HTML][HTML] Induction of skin fibrosis in mice expressing a mutated fibrillin-1 gene
S Saito, H Nishimura, RG Phelps, I Wolf, M Suzuki… - Molecular …, 2000 - Springer
S Saito, H Nishimura, RG Phelps, I Wolf, M Suzuki, T Honjo, C Bona
Molecular Medicine, 2000•SpringerBackground 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 …
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 …
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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