Mice carrying the tight skin (TSK) mutation harbors a 3.0-kb genomic duplication (exons 17–40) of the fibrillin-1 gene (Fbn-1) locatedon band F of chromosome 2 as TSK mutation. We cloned and sequenced the mutated Fbn-1 gene, since it is believed to be responsible for TSK syndrome. Sequence analysis showed numerous amino aciddifferences in the 5′ and 3′ segments between the TSK mutation and wild-type fbn-1 gene, but any amino acid difference between the TSK mutation and C57BL/6 mice. (TSK and C57Bl/6 mice are genetically similar, differing only by TSK mutation.) Four amino acid differences were observed between two copies of TSK's fbn-1 gene encoded by exons 17–40. Our results suggest that the majority of structural differences occurred in the N and C termini segments during strain divergence and only a few after the duplication event.