| | |  | | | | Record from Web of Science® | | | | | | |
| A FUNCTIONAL KNOCKOUT OF HUMAN KERATIN-14 |
|
|
| Author(s): RUGG EL, MCLEAN WHI, LANE EB, PITERA R, MCMILLAN JR, DOPPINGHEPENSTAL PJC, NAVSARIA HA, LEIGH IM, EADY RAJ |
| Source: GENES & DEVELOPMENT Volume: 8 Issue: 21 Pages: 2563-2573 Published: NOV 1 1994 |
| Times Cited: 115 References: 62 |
| Abstract: The importance of keratins and other intermediate filaments in the maintenance of tissue structure is emphasized by the discovery that many hereditary skin-blistering diseases are caused by mutations in keratin genes. Here, we describe a situation in which keratin 14 (K14) is missing altogether in the epidermis: A homozygous 2-nucleotide deletion in exon I of the K14 gene causes premature termination of the mRNA transcripts upstream from the start of the rod domain and results in a K14 null phenotype. In this individual no keratin intermediate filaments are visible in basal epidermal cells, although filaments are present in the upper layers of the epidermis. No compensating keratin expression is detected in vivo, and K14 mRNA is down-regulated. The individual, diagnosed as Kobner (generalized) EBS, suffers from severe widespread keratinocyte fragility and blistering at many body sites, but although the phenotype is severe, it is not lethal. This K14-/- phenotype confirms that only one K14 gene is expressed in human epidermis and provides an important model system for examining the interdependence of different keratin filament systems and their associated structures in the skin. |
| Document Type: Article |
| Language: English |
| Reprint Address: RUGG, EL (reprint author), UNIV DUNDEE, INST MED SCI, DEPT ANAT, CANC RES CAMPAIGN LABS, CRC, CELL STRUCT RES GRP, DUNDEE DD1 4HN, SCOTLAND |
Addresses:
1. UNIV DUNDEE, INST MED SCI, DEPT PHYSIOL, DUNDEE DD1 4HN, SCOTLAND
2. UNITED MED & DENT SCH, ST THOMAS HOSP, ST JOHNS INST DERMATOL, LONDON SE1 7EH, ENGLAND
3. ROYAL LONDON HOSP, COLL MED, EXPTL DERMATOL LABS, LONDON E1 6BL, ENGLAND |
| Publisher: COLD SPRING HARBOR LAB PRESS, 1 BUNGTOWN RD, PLAINVIEW, NY 11724 |
| Subject Category: Cell Biology; Developmental Biology; Genetics & Heredity |
| IDS Number: PR220 |
| ISSN: 0890-9369 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |