title: Characterization and expression analysis of the Spink5 gene, the mouse ortholog of the defective gene in Netherton syndrome.
abstract: 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.
authors.affiliation: INSERM U563, Purpan Hospital, Place du Dr Baylac, 31059 Toulouse Cedex 3, France.
authors.forename: Marie Florence
authors.initials: MF
authors.lastname: Galliano
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Roccasecca
authors.forename: Pascal
authors.initials: P
authors.lastname: Descargues
authors.forename: Alessia
authors.initials: A
authors.lastname: Micheloni
authors.forename: Elaine
authors.initials: E
authors.lastname: Levy
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zambruno
authors.forename: Marina
authors.initials: M
authors.lastname: D'Alessio
authors.forename: Alain
authors.initials: A
authors.lastname: Hovnanian
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002874:Chromosome Mapping; D018076:DNA, Complementary; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D017490:Ichthyosis, Lamellar / Q000235:genetics; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D015843:Serpins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D012867:Skin / Q000737:chemistry / Q000166:cytology; D013577:Syndrome; D014018:Tissue Distribution; D014158:Transcription, Genetic
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D015843:Serpins; C495972:Spink5 protein, mouse