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The Tight Skin Mouse: Demonstration Of Mutant Fibrillin-1 Production And Assembly Into Abnormal Microfibrils, Cay M. Kielty, Michael Raghunath, Linda D. Siracusa, Michael J. Sherratt, Reiner Peters, C. Adrian Shuttleworth, Sergio A. Jimenez

Selected Works of Sergio Jiménez, MD, MACR

Mice carrying the Tight skin (Tsk) mutation harbor a genomic duplication within the fibrillin-1 (Fbn 1) gene that results in a larger than normal in-frame Fbn 1 transcript. In this study, the consequences of the Tsk mutation for fibrillin-containing microfibrils have been examined. Dermal fibroblasts from Tsk/+ mice synthesized and secreted both normal fibrillin (approximately 330 kD) and the mutant oversized Tsk fibrillin-1 (approximately 450 kD) in comparable amounts, and Tsk fibrillin-1 was stably incorporated into cell layers. Immunohistochemical and ultrastructural analyses of normal and Tsk/+ mouse skin highlighted differences in the gross organization and distribution of microfibrillar arrays. Rotary …