Identification and characterization of a novel component of the cornified envelope, cornifelin.

Psoriasis is recognized as a chronic inflammatory disease characterized by epidermal hyperproliferation. To identify psoriasis-related genes, we compared the mRNA populations of normal and psoriatic skin. We identified one gene, designated as cornifelin, which showed increased expression in psoriatic skin. Human cornifelin contains 112 amino acids and is expressed in the uterus, cervix, and skin. In situ hybridization analysis demonstrated the presence of human cornifelin in the granular cell layer of the epidermis. To investigate the function of cornifelin, we established a transgenic mouse line overexpressing human cornifelin. Using these mice, we have shown that cornifelin is directly or indirectly cross-linked to at least two other cornified envelope proteins, loricrin and involucrin, in vivo. Overexpression of human cornifelin correlated with decreased loricrin expression and increased involucrin expression in the transgenic mouse. However, abnormality of epidermal differentiation was not observed in the transgenic mouse.

[1]  James T. Elder,et al.  Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel candidate regions (16q and 20p) by genome-wide scan. , 1997, Human molecular genetics.

[2]  N. Martinet,et al.  N1N8-bis(gamma-glutamyl)spermidine cross-linking in epidermal-cell envelopes. Comparison of cross-link levels in normal and psoriatic cell envelopes. , 1990, The Biochemical journal.

[3]  P. Riegman,et al.  Characterization of the human kallikrein locus. , 1992, Genomics.

[4]  G. Melino,et al.  The cornified envelope: a model of cell death in the skin. , 1998, Results and problems in cell differentiation.

[5]  S. Murthy,et al.  Tissue-specific and differentiation-appropriate expression of the human involucrin gene in transgenic mice: an abnormal epidermal phenotype. , 1993, Differentiation; research in biological diversity.

[6]  Teruyoshi Hishiki,et al.  BodyMap: a human and mouse gene expression database , 2000, Nucleic Acids Res..

[7]  A. Bowcock,et al.  The genetics of psoriasis: a complex disorder of the skin and immune system. , 1998, Human molecular genetics.

[8]  K. Fujishige,et al.  Striatum- and testis-specific phosphodiesterase PDE10A isolation and characterization of a rat PDE10A. , 1999, European journal of biochemistry.

[9]  K. Yoneda,et al.  Overexpression of human loricrin in transgenic mice produces a normal phenotype. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Franco Ameglio,et al.  Cytokines in psoriasis , 1999, International journal of dermatology.

[11]  K. Wang,et al.  Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region. , 2000, Gene.

[12]  R. Trembath,et al.  Identification of a novel psoriasis susceptibility locus at 1p and evidence of epistasis between PSORS1 and candidate loci , 2001, Journal of medical genetics.

[13]  D. Hohl Expression patterns of loricrin in dermatological disorders. , 1993, The American Journal of dermatopathology.

[14]  G. Pinkus,et al.  Involucrin expression in normal and neoplastic human skin: a marker for keratinocyte differentiation. , 1984, The Journal of investigative dermatology.

[15]  Sridhar Rao,et al.  KERATINS AND SKIN DISORDERS , 1996, Cell biology international.

[16]  N. Proudfoot,et al.  3′ Non-coding region sequences in eukaryotic messenger RNA , 1976, Nature.

[17]  T. Ohnishi,et al.  Expression profiling by iAFLP: A PCR-based method for genome-wide gene expression profiling. , 1999, Genome research.

[18]  F. Watt,et al.  Measurement of the rate of epidermal terminal differentiation: expression of involucrin by S-phase keratinocytes in culture and in psoriatic plaques. , 1987, The Journal of investigative dermatology.

[19]  E. Fisher,et al.  Evidence that a locus for familial psoriasis maps to chromosome 4q , 1996, Nature Genetics.

[20]  A. Steven,et al.  Quasi-normal cornified cell envelopes in loricrin knockout mice imply the existence of a loricrin backup system. , 2002, Journal of Investigative Dermatology.

[21]  P. Steinert,et al.  Bricks and mortar of the epidermal barrier , 1999, Experimental & Molecular Medicine.

[22]  A. Steven,et al.  Lessons from Loricrin-Deficient Mice , 2000, The Journal of cell biology.

[23]  Kousaku Okubo,et al.  Large scale cDNA sequencing for analysis of quantitative and qualitative aspects of gene expression , 1992, Nature Genetics.

[24]  J. Browne,et al.  Identification of a major susceptibility locus on chromosome 6p and evidence for further disease loci revealed by a two stage genome-wide search in psoriasis. , 1997, Human molecular genetics.

[25]  R. Eckert,et al.  S100A11, S100A10, Annexin I, Desmosomal Proteins, Small Proline-rich Proteins, Plasminogen Activator Inhibitor-2, and Involucrin Are Components of the Cornified Envelope of Cultured Human Epidermal Keratinocytes* , 1997, The Journal of Biological Chemistry.

[26]  H. Green,et al.  The cornified envelope of terminally differentiated human epidermal keratinocytes consists of cross-linked protein , 1977, Cell.

[27]  H. Green,et al.  Targeted Ablation of the Murine Involucrin Gene , 2000, The Journal of cell biology.

[28]  T. Wienker,et al.  Genomewide scan in german families reveals evidence for a novel psoriasis-susceptibility locus on chromosome 19p13. , 2000, American journal of human genetics.

[29]  B. Bernard,et al.  Abnormal sequence of expression of differentiation markers in psoriatic epidermis: inversion of two steps in the differentiation program? , 1988, The Journal of investigative dermatology.

[30]  Maria I Morasso,et al.  Suprabasin, a Novel Epidermal Differentiation Marker and Potential Cornified Envelope Precursor* , 2002, The Journal of Biological Chemistry.

[31]  K. Omori,et al.  Human Ca2+/calmodulin-dependent phosphodiesterase PDE1A: novel splice variants, their specific expression, genomic organization, and chromosomal localization. , 2001, Biochimica et biophysica acta.

[32]  B. Shroot,et al.  Morphological and biochemical characterization of the cornified envelopes from human epidermal keratinocytes of different origin. , 1988, The Journal of investigative dermatology.

[33]  Elaine Fuchs,et al.  Changes in keratin gene expression during terminal differentiation of the keratinocyte , 1980, Cell.