Matsuki M, Yamashita F, Ishida-Yamamoto A, Yamada K, Kinoshita C, Fushiki S, Ueda E, Morishima Y, Tabata K, Yasuno H, Hashida M, Iizuka H, Ikawa M, Okabe M, Kondoh G, Kinoshita T, Takeda J, Yamanishi K
Department of Dermatology, Research Institute for Neurological Diseases and Geriatrics, Kyoto Prefectural University of Medicine, Kyoto 602, Japan.
Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):1044-9. doi: 10.1073/pnas.95.3.1044.
The stratum corneum of the skin serves as an effective barrier for maintenance of the internal milieu against the external environment. At the cell periphery of the stratum corneum is the cell envelope, a highly insoluble membranous structure composed of precursor proteins cross-linked by epsilon-(gamma-glutamyl)lysine bonds. Transglutaminase 1 (TGase 1; keratinocyte TGase), a membrane-bound isozyme of the TGase family, has been proposed to catalyze this process of assembly. Deficient cross-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 suggest the importance of this gene in production of the cell envelope. In this study, we generated mice lacking the TGase 1 gene, and we report that they have erythrodermic skin with abnormal keratinization. In their stratum corneum, degradation of nuclei and keratohyalin F-granules was incomplete and cell envelope assembly was defective. The skin barrier function of TGase 1-null mice was markedly impaired, and these mice died within 4-5 h after birth. These results clearly demonstrate that 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 cases of LI.
皮肤的角质层作为一种有效的屏障，可维持体内环境免受外部环境的影响。在角质层细胞周边是细胞包膜，它是一种高度不溶性的膜状结构，由通过ε-（γ-谷氨酰）赖氨酸键交联的前体蛋白组成。转谷氨酰胺酶1（TGase 1；角质形成细胞TGase）是TGase家族的一种膜结合同工酶，已被认为催化这一组装过程。在一些患有常染色体隐性皮肤病板层状鱼鳞病（LI）的患者中，细胞包膜的交联不足，并且在LI家族中已鉴定出TGase 1基因的几种突变，这表明该基因在细胞包膜产生中的重要性。在本研究中，我们培育出了缺乏TGase 1基因的小鼠，并报告它们患有皮肤角化异常的红皮病。在它们的角质层中，细胞核和透明角质颗粒F的降解不完全，细胞包膜组装存在缺陷。TGase 1基因敲除小鼠的皮肤屏障功能明显受损，这些小鼠在出生后4 - 5小时内死亡。这些结果清楚地表明，TGase 1基因对于角质层的发育和成熟以及出生后适应环境至关重要。因此，这些TGase 1基因敲除小鼠可能是LI严重病例的有用模型。
