Overexpression of human loricrin in transgenic mice produces a normal phenotype.
The cornified cell envelope (CE) of terminally differentiating stratified squamous epithelial cells is a complex multiprotein assembly about 15 nm thick of which loricrin is a major component. We have produced transgenic mice bearing the human loricrin transgene in order to study the role of loricrin in CE assembly, structure, and function. By analyses of RNA and protein, we show that the human transgene is expressed in mouse epithelial tissues in an appropriate developmental manner but at an overall level about twice that of endogenous mouse loricrin. Thus the 20-kbp construct used contains all necessary regulatory elements. By immunogold electron microscopy, all of the expressed protein is incorporated into the CE. That no alternations were noted indicates that overproduction of the loricrin component of the CE does not affect the flexible structure or function of the epithelial tissues. Furthermore, these data imply that loricrin may be the last protein to be deposited onto, and thus lines, the intracellular surface of the CE, where it may be accessible to interact with the subjacent keratin intermediate-filament network.
Yoneda
K
K
Skin Biology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
Steinert
P M
PM
D000367:Age Factors; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000502:physiology; D002454:Cell Differentiation; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D004817:Epidermis / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D015870:Gene Expression; D005796:Genes; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic / Q000196:embryology; D008969:Molecular Sequence Data; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors; D014018:Tissue Distribution
D017931:DNA Primers; D008565:Membrane Proteins; D012333:RNA, Messenger; C064554:loricrin; D002118:Calcium