Keratin mutations and human skin disease

  • 217 Pages
  • 3.74 MB
  • English
Keratin., Skin -- Dise
Statementby Anthony G. Letai.
LC ClassificationsMicrofilm 94/3065 (Q)
The Physical Object
Paginationx, 217 leaves
ID Numbers
Open LibraryOL1242337M
LC Control Number94629465

Epidermal keratinocyte (KC), the major cell type in the skin epidermis, plays critical roles in forming a permeability barrier to separate internal organs from external stimuli. Keratins, constituting about 30–80% of the total protein in KCs, form the major intermediate filament cytoskeleton of KC.

Keratins consist of 54 unique genes in humans and they are expressed in cell- differentiation Cited by: 3. Introduction. The link between keratin intermediate filament proteins and inherited skin fragility disorders was first discovered in the early s and proved a turning point in our understanding of intermediate filament function.

The growing number of keratin mutations published over the last 10 years as associated causatively with human pathology (more than keratin mutations Cited by: The association of keratin mutations with genetic skin fragility disorders is now one of the best-established examples of cytoskeleton disorders.

It has served as a paradigm for many other diseases and has been highly informative for the study of intermediate filaments and. Keratin gene mutations in disorders of human skin and its appendages.

hair and hair follicle-specific keratins have been implicated in a wide range of hereditary diseases. The exact phenotype of each disease usually reflects the spatial expression level and the types of mutated keratin genes, the location of the mutations and their Cited by:   Mutations in keratin genes cause a diverse spectrum of skin, hair and mucosal disorders.

Cutaneous disorders include epidermolysis bullosa simplex, palmoplantar keratoderma, epidermolytic ichthyosis and pachyonychia congenita. Both clinical and laboratory observations confirm a major role for keratins in maintaining epidermal cell–cell by: Vassar R, Coulombe PA, Degenstein L, Albers K, Fuchs E.

Mutant keratin expression in transgenic mice causes marked abnormalities resembling a human genetic skin disease. Cell. Jan 25.

Molecular defects in cutaneous keratin genes encoding for keratin intermediate filaments (KIFs) causes keratinocytes and tissue-specific fragility, accounting for a large number of genetic disorders in human skin and its appendages.

These diseases are characterized by keratinocytes fragility (cytolysis), intra-epidermal blistering. The identification of causative pathogenic mutations in the keratin genes KRT5 and KRT14 in the human blistering skin disease epidermolysis bullosa simplex (EBS) changed this view and demonstrated the importance of these proteins for maintaining tissue resilience (Bonifas et al., ; Coulombe et al., ; Lane et al., ).

As the first. What we have learned from the study of keratin genes The genetics of human skin diseases Epstein Jr is that at least one factor underlying this localisation is the site-limited expression of the abnormal protein (Fig. 1) and surely this lesson of the `recognition' by disease processes of biochemical heterogeneity of different skin sites.

Mutations that perturb keratin filament assembly in vitro can cause blistering human skin disorders in vivo. From studies of these diseases, an important function of keratins has been unraveled. These filaments impart mechanical strength to a keratinocyte, without which the cell becomes fragile and prone to rupturing upon physical stress.

The human skin serves as a source for a large number of neurohormones and neuropeptides, which affect skin biology on multiple different levels. Intriguingly, this includes the control of keratin expression by neurohormones such as thyrotropin-releasing hormone, thyrotropin, opioids, prolactin, and cannabinoid receptor 1-ligands.

While this neuroendocrine regulation of human keratin. The long-term project also has researchers examining the role of mutations in keratin genes in certain genetic skin disorders. Approaches include gene cloning and analysis, and the use of transgenic mice to examine the effects of mutant keratins and to determine their relationship to known genetic diseases.

Keratin 1 (KRT1) and its heterodimer partner keratin 10 (KRT10) are major constituents of the intermediate filament cytoskeleton in suprabasal epidermis.

KRT1 mutations cause epidermolytic ichthyosis in humans, characterized by loss of barrier integrity and recurrent erythema. In search of the largely unknown pathomechanisms and the role of keratins in barrier formation and inflammation. Keratin mutations are associated with several skin, oral, esophageal, ocular, hair, and liver diseases that reflect the tissue-specific expression of the particular keratin (Fuchs and Cleveland, ; Omary et al., ).The resulting disease-related tissue defects are manifestations of the clearly defined function of keratins that allows cells to cope with mechanical stresses.

Since mutations in several keratin genes have been found to cause a variety of human diseases affecting the epidermis and other epithelial structures. Epidermolysis bullosa simplex (EBS) was the First mechanobullous disease for which the underlying genetic lesion was found, with mutations in both the K5 and K14 genes rendering basal.

The genetic mutations in keratin genes lead to errors during the complex assembly and differentiation process of the epidermis, leading to keratin-associated skin diseases. This is because the cytoskeletal system of keratin intermediate filaments (KIFs) is fundamental in the cytoplasm of keratinocytes.

The archetypal keratin disorder is the hereditary skin blistering disease epidermolysis bullosa simplex (EBS), caused by dominant mutations in either of the genes encoding keratins K5 or K This pair of type I and type II keratins (K14 and K5, respectively) are specifically expressed in a single layer of epithelial cells—the basal cell layer.

A major turning point came with the discoveries that mutations in keratin intermediate filament genes were responsible for a large number of inherited skin fragility disorders. These disease links showed unequivocally that intermediate filament proteins, at least in barrier epithelia like skin, provide essential stress resilience for cells in.

Keratin mutations are associated with several skin, oral, esophageal, ocular and cryptogenic liver diseases that reflect tissue-specific expression of the particular keratin involved (1–6).The resulting cellular and tissue defects are manifestations of the clearly defined function of keratins that provides cells with ability to cope with mechanical stresses.

Epidermolytic hyperkeratosis is an autosomal dominant blistering skin disease arising from mutations in the genes for keratin (K) 1 and The offspring of patients with epidermal nevi may have. This book presents, for the first time, a comprehensive overview on the strikingly manifold patterns and peculiarities of mosaic skin disorders.

genodermatosis caused by mutations in keratin 5. Disorders of keratinisation. Created Learning objectives. Describe common features of lichen planus, lichen sclerosus, ichthyosis, pityriasis rubra pilaris, Darier disease and keratosis pilaris Lichenoid diseases.

Details Keratin mutations and human skin disease FB2

Many skin diseases include the term ‘lichen’, which is thought to originate from a resemblance to the lichen that is found on trees. Dowling-Degos disease. At least five mutations in the KRT5 gene have been found to cause Dowling-Degos disease. This condition results in various skin abnormalities, including a characteristic lacy pattern of abnormally dark skin coloring (hyperpigmentation) that occurs mostly in.

The fundamental keratin functions are revealed in congenital human skin diseases caused by mutations in keratin genes, e.g., Epidermolysis bullosa simplex or Epidermolytic hyperkeratosis.

Most keratin gene mutations have a dominant-negative effect disrupting the filamentous structure formation even from the natural allele, and leaving the cell.

Handbook of Mouse Mutations with Skin and Hair Abnormalities presents 48 mouse mutations that are all available to the biomedical community.

Download Keratin mutations and human skin disease FB2

Many of the mouse mutations with dermatological diseases are reviewed and illustrated in detail. This popular reference book gives you a single source to use when determining which mouse mutation will best serve your needs as a biomedical tool for.

Epidermolysis bullosa simplex. More than 60 mutations in the KRT14 gene have been identified in people with epidermolysis bullosa simplex, a condition that causes the skin to be very fragile and to blister easily. Most of these genetic changes alter single protein building blocks (amino acids) used to make keratin A detailed section written by renowned experts compares the biology of human and mouse skin and skin diseases in the areas of development and the use of animal models, mammalian genetics, keratin biochemistry, epidermal and hair follicle cycles and kinetics, cytokines and growth factors, keratinocyte culture systems, cutaneous carcinogenesis.

In humans, the type I and II keratin gene clusters are located at chromosome 17q and 12q, respectively, and 54 functional keratin genes have been identified to date. 2 Many congenital skin diseases have been attributed to keratin mutations, such as epidermolysis bullosa simplex (OMIM ; genes KRT5 and KRT14) and epidermolytic.

Our findings add keratin 8 to the other “soft” keratins in which mutations have been associated with skin, oral, and ocular diseases. 8 Additional mutations in the gene for keratin 8 and. Such a functional role for keratin was not discernible before the use of transgenic animal models as was done first for K14 and subsequently several other IF proteins, and the initial identification of keratin mutations in the human blistering skin disease epidermolysis bullosa simplex (6, 13, 33).

There are many different keratin proteins normally expressed in the human integumentary system.

Description Keratin mutations and human skin disease EPUB

Mutations in keratin proteins in the skin can cause disease. Cutaneous conditions caused by mutations in keratin proteins Defective keratin type Condition(s) 1.

It is already well established that keratin mutations are responsible for a range of genetic skin diseases such as epidermolysis bullosa. Recently it has been shown that mutations in the gene for the skin protein filaggrin (of which many have now been found) can cause ichthyosis vulgaris [2], and that there may be a link between null mutations.Keratin intermediate filaments constitute the primary cytoskeletal component of epithelial cells.

Numerous human disease phenotypes related to keratin mutation remain mechanistically elusive. Our recent crystal structures of the helix 1B heterotetramer from keratin 1/10 enabled further investigation of the effect of pathologic 1B domain mutations on keratin structure.