Profiling gene expression changes in the epidermis of embryonic murine Harlequin Ichthyosis skin
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE56125 | GEO | 2014/09/16
SECONDARY ACCESSION(S): PRJNA242510
REPOSITORIES: GEO
Similar Datasets
Project description:Gene expression analysis of the epidermis from Lexicon Genetics Abca12 knockout mouse model of Harlequin Ichythois compared with wild type embryos to search for pathways specifically altered in the condition. Results indicate a large immune and inflammatory response occurs in the sterile environment of the uterus. Total RNA isolated from E17.5 back skin epidermis from murine Harlequin Ichthyosis model compared with wild type embryos.
2014-09-16 | E-GEOD-56125 | biostudies-arrayexpress
Project description:The biology of Harlequin Ichthyosis (HI), a devastating skin disorder, caused by loss of function mutations in the gene ABCA12, is poorly understood and to date no satisfactory treatment has been developed. We sought to investigate pathomechanisms of Harlequin Ichthyosis which could lead to the identification of safe and effective treatments to improve patients' quality of life. RNA-Seq analysis using normal skin (n=5) and HI patient skin (n=4) were performed to define the effects of loss of ABCA12. Functional annotation clustering analysis showed changes in three common groups: epidermal differentiation, lipid metabolism and inflammation (innate immunity and IFNγ signalling). In HI patient skin, gene expression of STAT1, STAT3 and Interleukin 36 (IL-36) A and G cytokines was significantly upregulated compared to normal skin, whereas IL-37, an inhibitor of innate immunity, was downregulated. RNA-Seq and functional assays were performed to define the effects of loss of ABCA12, using an engineered CRISPR-Cas9 ABCA12 KO 3D model. Functional annotation clustering analysis showed changes in three common groups: epidermal differentiation, lipid metabolism and inflammation.
2020-09-02 | GSE131903 | GEO
Project description:Autosomal recessive congenital ichthyoses (ARCI) are a group of non-syndromic congenital keratinization disorders including harlequin ichthyosis, lamellar ichthyosis, and congenital ichthyosiform erythroderma with a total prevalence of 1:200,000. Affected individuals who are often born as collodion babies present with generalized scaling of the skin. This reflects a physical compensation for the defective cutaneous permeability barrier underlying all ichthyoses. Inactivity of 12R-lipoxygenase (12R-LOX) is a frequent cause of ARCI. Epidermis-specific conditional knockout of Alox12b encoding 12R-LOX was established in mice using the Cre-Lox system. Tamoxifen-induced Alox12b inactivation in mouse skin caused an ichthyosis-like phenotype. We used microarray to compare the gene expression profile in the epidermis of mice after tamoxifen induced Alox12b inactivation with that of control animals. Inactivation of Alox12b was associated with the upregulation of genes involved in keratinization, cholesterol biosynthesis, and Fc-epsilon receptor signaling.
2019-03-01 | GSE127434 | GEO
Project description:Autosomal recessive congenital ichthyoses are a group of non-syndromic congenital keratinization disorders including harlequin ichthyosis, lamellar ichthyosis, and congenital ichthyosiform erythroderma with a total prevalence of 1:200,000. Affected individuals who are often born as collodion babies present with generalized scaling of the skin. This reflects a physical compensation for the defective cutaneous permeability barrier underlying all ichthyoses. Inactivity of 12R-lipoxygenase (12R-LOX) is a frequent cause of ARCI. Mice with targeted inactivation of the 12R-LOX gene Alox12b were established .Heterozygous mutant mice (Alox12b+/−) were bred with 129S6, and their heterozygous offspring were intercrossed to obtain homozygous mutant mice. Homozygous Alox12b knockout mice died within 3 hours after birth owing to defective skin barrier function. We used microarray to compare the gene expression profile in the epidermis of Alox12b-null mice with that of wildtype animals. Inactivation of Alox12b was associated with the upregulation of genes involved in keratinization, cholesterol biosynthesis, and Fc-epsilon receptor signaling.
2019-03-01 | GSE127435 | GEO
Project description:Profiling gene expression changes in the epidermis of embryonic murine Harlequin Ichthyosis skin
| PRJNA242510 | ENA
Project description:The purpose of this study was to analyze the genomic signatures and profiles of skin from ichthyosis (various subtypes) vs. healthy patients. The analysis strategy was to study differentially expressed genes common to the ichthyosis shared phenotype, as well as individual ichthyosis subtypes, and compare and contrast to the genomic profiles of atopic dermatitis and psoriasis.
2018-10-10 | GSE108640 | GEO
Project description:The cross-linked envelope of the mammalian epidermal corneocyte is important as a scaffold for assembly of the lipid barrier of the epidermis. Illustrating its importance, deficient envelope cross-linking by keratinocyte transglutaminase (TGM1) is a major cause of the autosomal recessive congenital ichthyoses, characterized by barrier defects. Expectations that loss of some of the known envelope protein components would also confer an ichthyosis phenotype have been difficult to demonstrate. To help rationalize this observation with one major component, the protein profile of epidermis from loricrin knockout mice has been compared to that of the wild type. Despite the mild phenotype of the knockout, some 40 proteins have been seen to be incorporated into envelope material to significantly different extents. Nearly half of these proteins were also seen to be incorporated to similarly altered extents into the disulfide bonded keratin network of the corneocyte. The results suggest that loss of loricrin alters their incorporation into envelopes as a consequence of protein-protein interactions during cell maturation. Mass spectrometric protein profiling revealed that keratin 1, keratin 10 and loricrin are prominent envelope components and that dozens of other proteins are also components. This finding helps rationalize the potential formation of functional envelopes despite loss of a single component due to availability of many alternative transglutaminase substrates
2016-12-14 | PXD003576 | Pride
Project description:The cross-linked envelope of the mammalian epidermal corneocyte is important as a scaffold for assembly of the lipid barrier of the epidermis. Illustrating its importance, deficient envelope cross-linking by keratinocyte transglutaminase (TGM1) is a major cause of the autosomal recessive congenital ichthyoses, characterized by barrier defects. Expectations that loss of some of the known envelope protein components would also confer an ichthyosis phenotype have been difficult to demonstrate. To help rationalize this observation with one major component, the protein profile of epidermis from loricrin knockout mice has been compared to that of the wild type. Despite the mild phenotype of the knockout, some 40 proteins have been seen to be incorporated into envelope material to significantly different extents. Nearly half of these proteins were also seen to be incorporated to similarly altered extents into the disulfide bonded keratin network of the corneocyte. The results suggest that loss of loricrin alters their incorporation into envelopes as a consequence of protein-protein interactions during cell maturation. Mass spectrometric protein profiling revealed that keratin 1, keratin 10 and filaggrin are prominent envelope components and that dozens of other proteins are minor components. This finding helps rationalize the potential formation of functional envelopes despite loss of a single component due to availability of many alternative transglutaminase substrates.
2016-12-14 | PXD003532 | Pride
Project description:We generated KA mutant mice (Krt14-CreERT + ABCA12-flox/flox) and controls (ABCA12-flox/flox) that enabled us to assess the effects of deleting a critical barrier gene, ABCA12, in the skin epidermis following tamoxifen treatment. These studies identified numerous differentially expressed genes (DEGs) upon barrier disruption/ABCA12 deletion, including compensatory upregulation of genes involved with epidermal differentiation and barrier function. Overall, this data-set provides a global view of molecular changes that occur in adult mouse skin following barrier perturbation.
2024-05-20 | GSE254889 | GEO