DEFECTIVE STRATUM-CORNEUM AND EARLY NEONATAL DEATH IN MICE LACKING THE GENE FOR TRANSGLUTAMINASE-1 (KERATINOCYTE TRANSGLUTAMINASE)

The stratum corneum of the skin serves as an effective barrier for mai ntenance of the internal milieu against the external environment. At t he cell periphery of the stratum corneum is the cell envelope, a highl y insoluble membranous structure composed of precursor proteins crossl inked by epsilon-(gamma-glutamyl)lysine bonds. Transglutaminase 1 (TGa se 1; keratinocyte TGase), a membrane-bound isozyme of the TGase famil y, has been proposed to catalyze this process of assembly. Deficient c ross-linking of the cell envelope in some patients with the autosomal recessive skin disorder lamellar ichthyosis (LI) and several mutations of the TGase 1 gene that have been identified in families with LI sug gest the importance of this gene in production of the cell envelope, I n this study, we generated mice lacking the TGase 1 gene, and we repor t that they have erythrodermic skin with abnormal keratinization. In t heir stratum corneum, degradation of nuclei and keratohyalin F-granule s was incomplete and cell envelope assembly was defective. The skin ba rrier function of TGase I-null mice was markedly impaired, and these m ice died within 4-5 h after birth. These results clearly demonstrate t hat the TGase 1 gene is essential to the development and maturation of the stratum corneum and to adaptation to the environment after birth, Thus, these TGase 1 knockout mice may be a useful model for severe ca ses of LI.