title: Gene targeting at the mouse cytokeratin 10 locus: severe skin fragility and changes of cytokeratin expression in the epidermis.
abstract: Bullous congenital ichthyosiform erythroderma (BCIE) is a dominantly inherited blistering skin disorder caused by point mutations in the suprabasal cytokeratins 1 or 10. Targeting the murine cytokeratin 10 gene in ES cells resulted in mice with different phenotypes in the homozygotes and heterozygotes; both of which exhibit similarities to specific clinical characteristics of BCIE. Homozygotes suffered from severe skin fragility and died shortly after birth. Heterozygotes were apparently unaffected at birth, but developed hyperkeratosis with age. In both genotypes, aggregation of cytokeratin intermediate filaments, changes in cytokeratin expression, and alterations in the program of epidermal differentiation were observed. In addition we demonstrate, for the first time, the existence of the murine equivalent of human cytokeratin 16.
authors.affiliation: Institute of Cell and Molecular Biology, University of Edinburgh.
authors.forename: R M
authors.initials: RM
authors.lastname: Porter
authors.forename: S
authors.initials: S
authors.lastname: Leitgeb
authors.forename: D W
authors.initials: DW
authors.lastname: Melton
authors.forename: O
authors.initials: O
authors.lastname: Swensson
authors.forename: R A
authors.initials: RA
authors.lastname: Eady
authors.forename: T M
authors.initials: TM
authors.lastname: Magin
mesh_terms: D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D018390:Gene Targeting; D005804:Genes, Lethal; D006579:Heterozygote; D006720:Homozygote; D017488:Hyperkeratosis, Epidermolytic / Q000209:etiology / Q000235:genetics* / Q000628:therapy; D053550:Keratin-10; D007633:Keratins / Q000032:analysis / Q000172:deficiency / Q000235:genetics* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012867:Skin / Q000473:pathology
chemical_list: C507493:KRT10 protein, human; C507491:Krt10 protein, mouse; D053550:Keratin-10; D007633:Keratins