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| POINT MUTATIONS IN HUMAN KERATIN-14 GENES OF EPIDERMOLYSIS-BULLOSA SIMPLEX PATIENTS - GENETIC AND FUNCTIONAL ANALYSES |
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| Author(s): COULOMBE PA, HUTTON ME, LETAI A, HEBERT A, PALLER AS, FUCHS E |
| Source: CELL Volume: 66 Issue: 6 Pages: 1301-1311 Published: SEP 20 1991 |
| Times Cited: 427 References: 50 |
| Abstract: Previously we demonstrated that transgenic mice expressing mutant basal epidermal keratin genes exhibited a phenotype resembling a group of autosomal dominant human skin disorders known as epidermolysis bullosa simplex (EBS). EBS diseases affect approximately 1: 50,000 and are of unknown etiology, although all subtypes exhibit blistering arising from basal cell cytolysis. We now demonstrate that two patients with spontaneous cases of Dowling-Meara EBS have point mutations in a critical region in one (K14) of two basal keratin genes. To demonstrate function, we engineered one of these point mutations in a cloned human K14 cDNA, and showed that a K14 with an Arg-125 --> Cys mutation disrupted keratin network formation in transfected keratinocytes and perturbed filament assembly in vitro. Since we had previously shown that keratin network perturbation is an essential component of EBS diseases, these data suggest that the basis for the phenotype in this patients resides in this point mutation. |
| Document Type: Article |
| Language: English |
| Reprint Address: COULOMBE, PA (reprint author), UNIV CHICAGO, HOWARD HUGHES MED INST, DEPT MOLEC GENET & CELL BIOL, CHICAGO, IL 60637 USA |
Addresses:
1. UNIV TEXAS, DEPT DERMATOL, HOUSTON, TX 77030 USA
2. NORTHWESTERN UNIV, CHILDRENS MEM HOSP, SCH MED, DEPT DERMATOL, CHICAGO, IL 60614 USA |
| Publisher: CELL PRESS, 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: GG552 |
| ISSN: 0092-8674 |
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