Form Of Autosomal Recessive Ichthyosis Research Articles

Essential Functions of Glycans in Human Epithelia Dissected by a CRISPR-Cas9-Engineered Human Organotypic Skin Model.

SummaryThe glycome undergoes characteristic changes during histogenesis and organogenesis, but our understanding of the importance of select glycan structures for tissue formation and homeostasis is incomplete. Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation. We used CRISPR-Cas9 gene targeting to generate a library of 3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids. This tissue library revealed distinct changes in skin formation associated with a loss of features for all tested glycoconjugates. The organotypic skin model provides phenotypic cues for the distinct functions of glycoconjugates and serves as a unique resource for further genetic dissection and identification of the specific structural features involved. The strategy is also applicable to other organotypic tissue models.

Transglutaminase 1 expression in a patient with features of harlequin ichthyosis: Case report

Harlequin ichthyosis (HI) is a life-threatening disorder characterized clinically by massive generalized hyperkeratosis and ultrastructurally by an absence of lamellar bodies. However, infants who survive the perinatal period develop a phenotype resembling the nonbullous ichthyosiform erythrodermic (CIE) form of autosomal recessive ichthyosis. We studied a child with a severe hyperkeratotic skin disorder present at birth that developed into a CIE-like phenotype. Electron microscopy demonstrated an absence of lamellar bodies consistent with HI. Abnormalities of filaggrin and involucrin expression by immunostaining were evident. However, transglutaminase 1 (TGase1) was expressed in the epidermis in a pattern consistent with other diseases that involve epidermal acanthosis. Analysis of patient keratinocytes grown in vitro demonstrated expression of normal amounts of TGase1 mRNA and full length TGase1 protein, as well as normal levels of transglutaminase enzymatic activity. (J Am Acad Dermatol 1998;38:325-9.)

Re‐expression of disease‐characteristic features of non‐bullous congenital ichthyosiform erythroderma (CIE) after graftig of the pathological keratinocyte cultures to athymic mice

Epidermal keratinocytes separated from skin lesions of non-bullous congenital ichthyosiform erythroderma were investigated in an attempt at experimental reproduction of this keratinization disorder. In vitro studies on growth and differentiation of pathological keratinocytes isolated from the influence of the host's dermal and humoral components were performed using the immersed epidermal cell culture technique. Ten to 25-day-old confluent and stratified cultures were examined by means of photonic and electron microscopy, and stained with various differentiation markers for indirect immunofluorescence studies. The cultured epidermis showed low-grade differentiation and no clear-cut evenly distributed signs of the original disease. Grafting on congenitally athymic nude mice allowed further differentiation of the epidermal sheets and re-expression of the histologic and ultrastructural features of non-bullous congenital ichthyosiform erythroderma. Thus, the purely epidermal origin of this particular form of autosomal recessive ichthyosis could be confirmed. Large amounts of pathological keratinocytes generated from small skin biopsies may be used for experimental purposes after grafting on several athymic animals.