Mice carrying the Tight skin (Tsk) mutation have thickened skin and visceral fibrosis resulting from an accumulation of extracellular matrix molecules. These and other connective tissue abnormalities have made Tskl + mice models for scleroderma, hereditary emphysema, and myocardial hypertrophy. Previously we localized Tsk to mouse chromosome 2 in a region syntenic with human chromosome 15. The microfibrillar glycoprotein gene, fibrillin 1 (FBN1), on human chromosome 15q, provided a candidate for the Tsk mutation. We now demonstrate that the Tsk chromosome harbors a 30- to 40-kb genomic duplication within the Fbn1 gene that results in a larger than normal in-frame Fbn1 transcript. These findings provide hypotheses to explain some of the phenotypic characteristics of Tskl + mice and the lethality of Tsk/Tsk embryos.
Recommended CitationSiracusa, Linda D.; McGrath, Rodney; Ma, Qing; Moskow, John J.; Manne, Jayanthi; Christner, Paul J.; Buchberg, Arthur M.; and Jimenez, Sergio A., "A tandem duplication within the fibrillin 1 gene is associated with the mouse tight skin mutation." (1996). Department of Medicine Faculty Papers. Paper 190.