Loricrin Gene Research Articles

Tissue-, differentiation- and developmental-specific expression of the human loricrin gene in transgenic mice

Tissue-, differentiation- and developmental-specific expression of the human loricrin gene in transgenic mice

Mapping of the Trichohyalin Gene: Co-Localization with the Profilaggrin, Involucrin, and Loricrin Genes

The chromosomal location of the gene encoding the human hair follicle protein trichohyalin has been determined by in situ hybridization. The human gene has been localized to the region 1q21.1-1q23 (probably 1q21.3) using a sheep trichohyalin cDNA probe. The genes encoding three other epithelial proteins, namely, profilaggrin, involucrin, and loricrin, are also located in the same region of chromosome 1, which, together with their similar gene and protein structures, suggests that the four proteins form a novel superfamily of epithelial structural proteins.

The cornified cell envelope: loricrin and transglutaminases.

The cornified cell envelope (CE) of terminally differentiated human epidermis is a complex structure consisting of several defined protein constituents. The CE is the most insoluble component of the epidermis due to crosslinking by disulfide bonds as well as isodipeptide bonds that are formed by the action of transglutaminases (TGases). We have recently determined that loricrin is the major component of CE. We now have isolated and characterized its gene and showed that it has a simple structure with a single intron. We also show that the loricrin gene maps to position 1q21, which, coincidentally, is similar to the location of the profilaggrin and involucrin genes. Human loricrin in 26 kDa and consists of three long glycine-serine-cysteine rich sequence domains that contain quasi-repeating peptides and which form the novel glycine loop motif. These are interspersed by lysine+glutamine rich domains involved in isodipeptide crosslinks. The glycine loops are thought to be involved in organization of epidermal proteins and maintenance of the flexibility of the epidermis. By use of PCR analyses, we have found that human loricrin consists of two allelic size variants, due to sequence variations in the second glycine loop domain only, and these variants segregate in the human population by normal Mendelian mechanisms. Furthermore, there are multiple sequence variants within these two size class alleles due to various deletions of 12 bp (4 amino acids) in the major loop of this glycine loop domain. In order to study the expression and role of TGases in the formation of CE, we have isolated and sequenced cDNA and genomic clones encoding the TGase1 enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

The human loricrin gene.

Loricrin is the major protein component of the cornified cell envelope of terminally differentiated mammalian epidermal (stratum corneum) cells. Using a specific human cDNA clone, we have isolated and characterized the human loricrin gene. We show that it has a very simple structure of a single intron of 1188 base pairs (bp) in the 5'-untranslated region; there are no introns in coding sequences. By use of rodent-human somatic cell hybrids, followed by in situ hybridization with a biotin-labeled genomic DNA clone, the single-copy gene maps to chromosome location 1q21. Polymerase chain reaction analyses of genomic DNAs from different individuals show that human loricrin consists of two allelic size variants, due to sequence variations in its second glycine loop domain, and these variants segregate in the human population by normal Mendelian mechanisms. Furthermore, there are multiple sequence variants within these two size class alleles due to various deletions of 12 bp (4 amino acids) in the major loop of this glycine loop domain. By use of a specific loricrin antibody, we show by immunogold electron microscopy that loricrin initially appears in the granular layer of human epidermis and forms composite keratohyalin granules with profilaggrin, but localizes to the cell periphery (cell envelope) of fully differentiated stratum corneum cells.

Transcription of the Human Loricrin Gene In Vitro Is Induced by Calcium and Cell Density and Suppressed by Retinoic Acid

We have previously shown that loricrin is a major component of the cornified cell envelope (CE) expressed late in epidermal differentiation in the granular layers of normal skin. Normal human keratinocytes were cultured under various conditions and loricrin mRNA levels were assessed at various time points. Only Ca++ concentrations above 0.1 mM Ca++ were permissive for the expression of lori-crin mRNA. Maximal mRNA levels were found at 0.35 mM Ca++ and a critical cell density appeared to be required for optimal accumulation of loricrin transcripts. Retinoic acid (RA) at 10(-7) to 10(-9) M completely blocked Ca+(+)-induced loricrin mRNA synthesis when applied simultaneously. Furthermore, addition of RA to cultures already exposed to higher Ca++ levels resulted in the complete loss of loricrin mRNA within 48-72 h. So far, no other components of the CE have been shown to be suppressed by RA. However, similar patterns of expression were reported for filaggrin, a matrix protein also expressed late in epidermal differentiation. Therefore, we compared the mRNA levels of loricrin and filaggrin and found them to change in parallel in response to the various culture conditions. These results suggest that Ca++, cell density, and RA are crucial regulators of loricrin expression in vitro and that the transcriptional control of loricrin and filaggrin expression in the epidermis are closely coordinated.