Galliano Marie Florence, Roccasecca Rosa Maria, Descargues Pascal, Micheloni Alessia, Levy Elaine, Zambruno Giovanna, D'Alessio Marina, Hovnanian Alain
INSERM U563, Purpan Hospital, Place du Dr Baylac, 31059 Toulouse Cedex 3, France.
Genomics. 2005 Apr;85(4):483-92. doi: 10.1016/j.ygeno.2005.01.001.
The human SPINK5 gene, encoding the putative 15-domain serine protease inhibitor LEKTI, was identified as the defective gene in the severe autosomal recessive ichthyosiform skin disorder known as Netherton syndrome and as a candidate susceptibility gene for atopic disease. Here we report mapping of the murine Spink5 gene to chromosome 18 and its characterization. We show that, unlike in humans, transcription of the mouse Spink5 gene generates two mRNAs that differ in the 3' untranslated region. The encoded protein, which is detected in differentiated primary cultured keratinocytes and mouse skin as an approximately 130-kDa glycosylated precursor, displays approximately 60% identity with its human counterpart but lacks the human LEKTI domain 6. As in the human, mouse Lekti represents a marker of epithelial differentiation, strongly expressed in the granular layer of the epidermis, in suprabasal layers of stratified epithelia, and in thymic Hassall's bodies. Our data indicate that mouse Spink5/Lekti, like its human counterpart, is involved in the control of epithelial tissue homeostasis, but also highlight specific features of the murine gene and protein.
人类SPINK5基因编码假定的含15个结构域的丝氨酸蛋白酶抑制剂LEKTI，该基因被确定为严重常染色体隐性鱼鳞病样皮肤疾病（即Netherton综合征）中的缺陷基因，也是特应性疾病的候选易感基因。在此，我们报告了小鼠Spink5基因定位于18号染色体及其特征。我们发现，与人类不同，小鼠Spink5基因转录产生两种在3'非翻译区不同的mRNA。编码的蛋白质在分化的原代培养角质形成细胞和小鼠皮肤中作为一种约130 kDa的糖基化前体被检测到，与人类对应物显示出约60%的同源性，但缺少人类LEKTI结构域6。与人类一样，小鼠Lekti是上皮分化的标志物，在表皮颗粒层、复层上皮的基底层以上以及胸腺哈氏小体中强烈表达。我们的数据表明，小鼠Spink5/Lekti与其人类对应物一样，参与上皮组织稳态的调控，但也突出了小鼠基因和蛋白质的特定特征。
