| First Author | Siracusa LD | Year | 1995 |
| Journal | 9th International Mouse Genome Conference | Pages | 17 (Abstr. 5) |
| Mgi Jnum | J:32746 | Mgi Id | MGI:80234 |
| Citation | Siracusa LD, et al. (1995) The molecular basis of the mouse tight skin (Tsk) mutation reveals its relationship to the microfibrillar protein, Fibrillin 1 (Fbn1). 9th International Mouse Genome Conference :17 (Abstr. 5) |
| abstractText | Full text of Abstract: 5. THE MOLECULAR BASIS OF THE MOUSE TIGHT SKIN (Tsk) MUTATION REVEALS ITS RELATIONSHIP TO THE MICROFIBRILLAR PROTEIN, FIBRILLIN 1 (Fbnl). Linda D. Siracusa1, Rodney McGrath2, Qing Ma1, Jayanthi Mannel, John J. Moskow1, Paul J. Christner2, Arthur M. Buchberg1, Sergio A. Jimenez2. lDepartment of Microbiology and Immunology, Jefferson Cancer Institute; 2Department of Medicine, Jefferson Medical College, 233 South 10th Street, Philadelphia, PA, 19107. Mice heterozygous for the spontaneous Tsk mutation display thickened skin and enlarged skeletons. Most organs exhibit an overabundance of extracellular matrix proteins. Embryos homologous for Tsk die at ~8 days in utero. Tsk/+ mice have served as models for the study of connective tissue diseases such as scleroderma, myocardial hypertrophy and hereditay emphysema. As a first step towards identifying the gene responsible for the Tsk mutation, we mapped Tsk with respect to molecular markers on chromosome 2. The cosegregation of the Fbnl gene with Tsk led us to investigate the candidacy of Fbnl. We isolated and sequenced mouse Fbnl cDNA clones and identified differences in Fbnl expression between Tsk/+ and +/+ mice. In addition, we searched for genomic alterations specific for Tsk and have now defined the molecular basis and genetic lesion responsible for the Tsk mutation. The conclusions lead to a unifying hypothesis for the diverse phenotypes observed in Tsk mice. (Research supported by NIH grants AR32564 and DK45717. LDS is the recipient of an ACS JFRA.) |
