Biomedical subjects

J Uitto

Publications and source records attributed to J Uitto.

At least 181 records · Page 10Linked to original sources

PubMed1997

Mutation-based prenatal diagnosis of Herlitz junctional epidermolysis bullosa.

Epidermolysis bullosa (EB) is a group of heritable diseases which manifest with blistering and erosions of the skin and mucous membranes. Due of life-threatening complications and significant long-term morbidity associated with the severe, neonatal lethal (Herlitz) form of junctional EB (H-JEB), there has been a demand for prenatal diagnosis from families at risk for recurrence. Previously, the only reliable method of prenatal diagnosis of EB was a fetal skin biopsy performed at 16-20 weeks' gestation and analysed by electron microscopy. Recently, the genes LAMA3, LAMB3, and LAMC2, encoding the polypeptide subunits of laminin 5, an anchoring filament protein, have been shown to contain mutations in H-JEB. In this study, direct detection of pathogenetic mutations in the laminin 5 genes was used to perform polymerase chain reaction (PCR)-based prenatal testing. DNA was obtained by chorionic villus sampling (CVS) at 10-15 weeks or amniocentesis at 12-19 weeks' gestation in 15 families at risk for recurrence of JEB. In 13 cases, the fetus was predicted to be either genetically normal or a clinically unaffected carrier of a mutation in one allele. These predictions have been validated in all cases by the birth of a healthy child. In two cases, an affected fetus was predicted, and the diagnosis was confirmed by subsequent fetal skin biopsy. These results demonstrate that DNA-based prenatal testing offers an early, expedient, and accurate method of prenatal diagnosis or an exclusion of Herlitz JEB.

Amniotic Fluid↗

PubMed1997

Genomic organization of the integrin beta 4 gene (ITGB4): a homozygous splice-site mutation in a patient with junctional epidermolysis bullosa associated with pyloric atresia.

Integrin beta 4 is expressed primarily within the epithelial basement membranes, and it contributes to the stable association of epidermis with the underlying basement membrane. Previous observations have suggested that the expression of this integrin, which is alternatively spliced in various cell types, is deficient in a variant of junctional epidermolysis bullosa associated with pyloric atresia (JEB-PA). To facilitate identification of mutations in the human beta 4 integrin gene, ITGB4, we have now determined its intron-exon organization. The entire gene was shown to consist of 41 exons spanning 36 kb of the genomic DNA on chromosome 17q11-qter. The mutation detection, using PCR-amplification of each exon followed by heteroduplex analysis, revealed a homozygous splicing mutation in a patient with JEB-PA. RT-PCR revealed the presence of two splice variants generated through utilization of cryptic splice sites, and both mRNA transcripts resulted in a frame-shift and premature termination codon of translation. The presence of the mutation resulted in dramatic reduction of the corresponding mRNA transcript level. Because beta 4 integrin is expressed not only in the skin but also in the epithelial lining of the stomach, the absent expression of this integrin in the proband may explain the blistering tendency and development of pyloric atresia.

Amino Acid Sequence↗

PubMed1997

A recurrent laminin 5 mutation in British patients with lethal (Herlitz) junctional epidermolysis bullosa: evidence for a mutational hotspot rather than propagation of an ancestral allele.

The three genes (LAMA3, LAB3 and LAMC2) that encode the anchoring filament protein, laminin 5, may all harbour pathogenetic mutations in the autosomal recessive blistering skin disorder, junctional epidermolysis bullosa (JEB). Recently, one particular mutation, R635X in the LAMB3 gene, has been found to account for approximately 40% of all JEB laminin 5 mutations (Kivirikko et al., Hum Mol Genet 1996; 5: 231-7). In this study, we assessed the frequency of this mutation in 12 British patients with lethal (Herlitz) JEB using PCR amplification of genomic DNA and restriction endonuclease digestion. The mutation R635X was fond in seven of 24 (29%) mutant alleles, confirming its relative frequency within the British gene pool. In addition, haplotype analysis using intragenic polymorphisms showed that the mutation arose on at least four different haplotype backgrounds, suggesting it represents a mutational hotspot rather than propagation of a common British ancestral allele. These findings support the hypermutable nature of this CpG dinucleotide and have implications in screening for laminin 5 gene mutations in British and other patients with JEB.

Alleles↗

PubMed1997

Immunohistochemical analysis of the skin in junctional epidermolysis bullosa using laminin 5 chain specific antibodies is of limited value in predicting the underlying gene mutation.

The anchoring filament protein laminin 5 is composed of three polypeptide chains (alpha 3, beta 3 and gamma 2) each encoded by separate genes (LAMA3, LAMB3 and LAMC2, respectively). Mutations in any of these three genes may give rise to the autosomal recessive blistering skin disease, junctional epidermolysis bullosa. At present, there is no easy way of predicting which of these three genes might harbour the pathogenetic laminin 5 mutations in a case of junctional epidermolysis bullosa. In this study, we assessed whether immunohistochemistry might be helpful in this regard. We performed immunohistochemical labelling of the dermal-epidermal junction using alpha 3, beta 3 and gamma 2 chain-specific antibodies in 11 patients with junctional epidermolysis bullosa, in whom the laminin 5 mutations had been previously delineated. Although, labelling for the laminin 5 chain bearing the mutations was attenuated or undetectable in all cases, a complete absence of labelling or a reduction in the staining intensity for the other two chains was also seen in all cases. The results showed that immunohistochemical labelling of the dermal-epidermal junction using alpha 3, beta 3 and gamma 2 chain-specific antibodies is not a specific indicator for which of the laminin 5 chain genes contains the pathogenetic mutations, and is therefore unreliable in screening for individual laminin 5 gene mutations in cases of junctional epidermolysis bullosa.

Adolescent↗

PubMed1997

Immunohistochemical, ultrastructural, and molecular features of Kindler syndrome distinguish it from dystrophic epidermolysis bullosa.

BACKGROUND: Kindler syndrome is a rare, inherited skin disease characterized by acral bullae formation, fusion of fingers and toes, and generalized progressive poikiloderma. The purpose of this study was to clarify the nature of the bullous component of Kindler syndrome and to determine whether this inherited skin disorder represents a variant of dystrophic epidermolysis bullosa or a unique independent clinical entity. OBSERVATIONS: Two unrelated patients with Kindler syndrome were studied. Electron microscopy demonstrated marked duplication of the lamina densa, and clefts were observed in areas where the lamina densa was destroyed or obscured. Hemidesmosomes and anchoring fibrils showed normal features. Indirect immunofluorescence revealed normal linear labeling with antibodies against hemidesmosomal components (alpha 6 and beta 4 integrins, BPAG1, and BPAG2) and against anchoring filament components such as uncein, as detected by the 19-DEJ-1 monoclonal antibody. However, antibodies against the 3 respective laminin 5 chains, type IV collagen, and various type VII collagen epitopes (the aminoterminal NC1 domain, the central triple helical collagenous domain, and the carboxyterminal end of the triple helical collagenous domain) revealed a broad reticular staining pattern. Molecular screening of the type VII collagen gene (COL7A1) in the patients and their parents by heteroduplex analysis failed to detect any band shifts indicative of pathologic mutations. CONCLUSIONS: These results suggest that the bullous component of Kindler syndrome is distinct from dystrophic epidermolysis bullosa caused by mutations in the type VII collagen gene. Additionally, the differential distribution patterns of uncein and laminin 5 in the patients' skin samples support the hypothesis that uncein and laminin 5 are different molecules.

Adult↗

PubMed1997

Recessive epidermolysis bullosa simplex associated with plectin mutations: infantile respiratory complications in two unrelated cases.

Plectin is a 500 kDa protein involved in cytoskeleton-plasma membrane attachment with a wide tissue distribution including cutaneous and airway epithelia, muscle and neuronal tissue. Recently, mutations in the gene encoding plectin (PLEC1) have been implicated in the pathogenesis of an autosomal recessive variant of epidermolysis bullosa simplex in which cutaneous blistering starting in the neonatal period is associated with muscular dystrophy in later life. In this study, we report two unrelated patients, both of consanguineous parentage, who presented with cutaneous blistering and a hoarse cry from birth. Both experienced inspiratory stridor and respiratory distress, necessitating emergency tracheostomy in one case. Immunoreactivity to monoclonal antibodies against plectin was absent or markedly reduced in skin biopsies from both patients. Electron microscopy revealed a low intraepidermal plane of cleavage and hypoplastic hemidesmosomes with a reduced association with keratin intermediate filaments. Direct sequencing of PLEC1 in each case demonstrated two novel homozygous frameshift deletion mutations, 5069del19 and 5905del2, which both create downstream premature termination codons. Although currently neither patient has symptoms of muscle disease, the identification of mutations in PLEC1 may be predictive for the future development of muscular dystrophy. Recessive epidermolysis bullosa simplex resulting from abnormalities in plectin should be considered in the differential diagnosis blistering, hoarseness and stridor in infancy.

Child, Preschool↗

PubMed1996

A homozygous nonsense mutation in the PLEC1 gene in patients with epidermolysis bullosa simplex with muscular dystrophy.

Plectin is a widely expressed cytomatrix component involved in the attachment of the cytoskeleton to the plasma membrane. We have recently reported that the skin and muscles of three patients affected by epidermolysis bullosa simplex with muscular dystrophy (MD-EBS), a genetic disorder characterized by skin blistering associated with muscle involvement, are not reactive with antibodies specific to plectin. We demonstrated that in the skin, lack of plectin leads to failure of keratin filaments to connect to the plasma membrane via the hemidesmosomes, whereas in the muscle the deficient expression of the molecule correlates with an aberrant localization of desmin in the muscle fibers. In this study we demonstrate that in a MD-EBS kindred with two affected members, the disease results from a homozygous nonsense mutation in the plectin (PLEC1) gene leading to a premature stop codon (CGA to TGA) and decay of the aberrant plectin messenger RNA. The segregation of the mutated allele implicates the mutation in the pathology of the disorder. These results confirm the critical role of plectin in providing cell resistance to mechanical stresses both in the skin and the muscle.

Alleles↗

PubMed1996

Identification of a bimodal regulatory element encompassing a canonical AP-1 binding site in the proximal promoter region of the human decorin gene.

We have previously described a tumor necrosis factor alpha (TNF-alpha) response element, located between residues -188 and -140 of the human decorin promoter, that mediates the inhibitory effect of TNF-alpha on decorin gene expression (Mauviel, A., Santra, M., Chen, Y.-Q., Uitto, J., and Iozzo, R. V. (1995) J. Biol. Chem. 270, 11692-11700). In this report, we demonstrate that interleukin 1 (IL-1), a pleiotropic cytokine that shares a wide variety of biological properties with TNF-alpha, uses the same cis element to up-regulate decorin gene expression. Specifically, IL-1 enhances the expression of the human decorin gene, and this effect is mediated by activation of the corresponding promoter, as shown in transient cell transfection experiments using decorin promoter-chloramphenicol acetyl transferase reporter gene constructs. Additional transfection experiments with various 5'-deletion promoter-chloramphenicol acetyltransferase constructs demonstrate that both the inhibitory effect of TNF-alpha and the stimulatory effect of IL-1 are mediated by a 48-base pair segment of the promoter, between residues -188 and -140. This region, which contains a canonical AP-1 binding site, TGAGTCA, allows an antagonistic effect of these two cytokines on the decorin promoter activity. When cloned upstream of the thymidine kinase promoter, this promoter fragment requires the AP-1 sequence to be responsive to IL-1. Supershift assays with various AP-1 antibodies identified c-Jun, Jun-B, and Fra-1 as components of the complex binding to the decorin promoter. Overexpression of c-jun, an oncogene encoding the c-Jun/AP-1 transcription factor, reduces the basal activity of both decorin and -188/-140 thymidine kinase promoter constructs. In contrast, blockage of c-jun expression with an antisense c-jun construct potentiates the stimulatory effect of IL-1 and reverses the response to TNF-alpha. These data indicate that the region between residues -188 and -140 of the human decorin promoter functions as a bimodal regulatory element and allows transcriptional repression by c-Jun/AP-1 complexes.

Binding Sites↗

PubMed1996

Cloning of the gene for human pemphigus vulgaris antigen (desmoglein 3), a desmosomal cadherin. Characterization of the promoter region and identification of a keratinocyte-specific cis-element.

Pemphigus vulgaris antigen is a cadherin-like desmosomal cell adhesion molecule expressed primarily in suprabasal keratinocytes within the epidermis. Previously characterized structural features have defined this molecule as a desmoglein, DSG3. In this study, we have cloned the human DSG3 gene and examined the transcriptional regulation of its expression. The total gene consisted of 15 exons and was estimated to span >23 kilobases. Comparison of exon-intron organization of DSG3 with bovine DSG1 and several classical cadherin genes revealed striking conservation of the structure. Up to 2.8 kilobases of the upstream genomic sequences were sequenced and found to contain several putative cis-regulatory elements. The promoter region was GC-rich and TATA-less, similar to previously characterized mammalian cadherin promoters. The putative promoter region was subcloned into a vector containing chloramphenicol acetyl transferase reporter gene. Transient transfections with a series of deletion clones indicated that the DSG3 promoter demonstrated keratinocyte-specific expression, as compared with dermal fibroblasts examined in parallel, and fine mapping identified a 30-base pair segment at -200 to -170 capable of conferring epidermal specific expression. The results provide evidence for the transcriptional regulation of the pemphigus vulgaris antigen gene, potentially critical for development of the epidermis and physiologic terminal differentiation of keratinocytes.

Amino Acid Sequence↗

PubMed1996

Loss of plectin causes epidermolysis bullosa with muscular dystrophy: cDNA cloning and genomic organization.

Plectin is a widely expressed high molecular weight protein that is involved in cytoskeleton-membrane attachment in epithelial cells, muscle, and other tissues. The human autosomal recessive disorder epidermolysis bullosa with muscular dystrophy (MD-EBS) shows epidermal blister formation at the level of the hemidesmosome and is associated with a myopathy of unknown etiology. Here, plectin was found to be absent in skin and cultured keratinocytes from an MD-EBS patient by immunofluorescence and immunoprecipitation, suggesting that plectin is a candidate gene/protein system for MD-EBS mutation. The 14800-bp human plectin cDNA was cloned and sequenced. The predicted 518-kD polypeptide has homology to the actin-binding domain of the dystrophin family at the amino terminus, a central rod domain, and homology to the intermediate filament-associated protein desmoplakin at the carboxyl terminus. The corresponding human gene (PLEC1), consisting of 33 exons spanning >26 kb of genomic DNA was cloned, sequenced, and mapped to chromosomal band 8q24. Homozygosity by descent was observed in the consanguineous MD-EBS family with intragenic plectin polymorphisms. Direct sequencing of PCR-amplified plectin cDNA from the patient's keratinocytes revealed a homozygous 8-bp deletion in exon 32 causing a frameshift and a premature termination codon 42 bp downstream. The clinically unaffected parents of the proband were found to be heterozygous carriers of the mutation. These results establish the molecular basis of MD-EBS in this family and clearly demonstrate the important structural role for plectin in cytoskeleton-membrane adherence in both skin and muscle.

Actins↗

PubMed1996

Cell-specific induction of distinct oncogenes of the Jun family is responsible for differential regulation of collagenase gene expression by transforming growth factor-beta in fibroblasts and keratinocytes.

Transforming growth factor-beta (TGF-beta) plays a major role in regulating connective tissue deposition by controlling both extracellular matrix production and degradation. In this study, we show that TGF-beta transcriptionally represses both basal and tumor necrosis factor-alpha-induced collagenase (matrix metalloprotease-1) gene expression in dermal fibroblasts in culture, whereas it activates its expression in epidermal keratinocytes. We demonstrate that this differential effect of TGF-beta on collagenase gene expression is due to a cell type-specific induction of distinct oncogenes of the Jun family, which participate in the formation of AP-1 complexes with different trans-activating properties. Specifically, our data indicate that the inhibitory effect of TGF-beta in fibroblasts is likely to be mediated by jun-B, based on the following observations: (a) TGF-beta induces high levels of jun-B expression and (b) over-expression of jun-B mimics TGF-beta effect in inhibiting basal collagenase promoter activity and preventing tumor necrosis factor-alpha-induced trans-activation of the collagenase promoter. In contrast, TGF-beta induction of collagenase gene expression in keratinocytes is preceded by transient elevation of c-jun proto-oncogene expression. Over-expression of c-jun leads to trans-activation of the collagenase promoter in both cell types, suggesting that c-jun is a ubiquitous inducer of collagenase gene expression. Transfection of keratinocytes with an antisense c-jun construct together with a collagenase promoter/reporter gene construct inhibits basal and TGF-beta-induced up-regulation of the collagenase promoter activity, implying that c-jun mediates TGF-beta effect in this cell type. Collectively, our data suggest differential signaling pathways for TGF-beta in dermal fibroblasts and epidermal keratinocytes, leading to cell type-specific induction of two AP-1 components with opposite transcriptional activities.

3T3 Cells↗

PubMed1996

An AP-1 binding sequence is essential for regulation of the human alpha2(I) collagen (COL1A2) promoter activity by transforming growth factor-beta.

Previous studies have shown that transforming growth factor-beta (TGF-be ta) and tumor necrosis factor-alpha (TNF-alpha) modulate type I collagen gene expression in fibroblasts. To fine-map the corresponding response elements in the human alpha2(I) collagen (COL1A2) promoter, we have generated a series of 5' deletion promoter/chloramphenicol acetyltransferase (CAT) reporter gene constructs. Transient cell transfection assays using human dermal fibroblasts and stable transfection experiments using NIH 3T3 fibroblasts identified the region located between residues -265 and -241, as critical for TGF-beta response. Specifically, we demonstrate that this 25-base pair region mediates the up-regulatory effect of TGF-beta on COL1A2 promoter activity and allows antagonistic activity of TNF-alpha on the TGF-beta effect. Gel mobility shift assays indicate that nuclear factor binding to this 25-base pair region of COL1A2 promoter is competed by AP-1, but not NF-1 or NF-kappaB, oligonucleotides. Transient cell transfection experiments with plasmid constructs in which the potential AP-1-binding site located within this short region of promoter was modified by site-directed mutagenesis indicated that this element plays a significant role in the basal activity of the promoter. Furthermore, this sequence is essential for TGF-beta response and does not require the presence of the three Sp-1-binding sites located further upstream, between nucleotides -273 and -304. In addition, overexpression of c-jun in co-transfection experiments with COL1A2 promoter/CAT constructs blocks the TGF- beta response, further implicating AP-1 in the regulation of COL1A2 gene expression. Our results clarify the molecular mechanisms involved in the regulation of type I collagen gene expression and further emphasize the importance of AP-1 in mediating some of the TGF-beta effects on gene transcription.

Base Sequence↗

PubMed1996

Molecular complexity of the cutaneous basement membrane zone.

Ultrastructural examination of the cutaneous basement membrane zone (BMZ) reveals the presence of several attachment structures, which are critical for integrity of the stable association of epidermis and dermis. These include hemidesmosomes which extend from the intracellular compartment of the basal keratinocyte to the underlying basement membrane where they complex with anchoring filaments, thread-like structures traversing the lamina lucida. At the lower portion of dermal-epidermal attachment zone, anchoring fibrils extend from the lamina densa to the papillary dermis, where they associate with basement membrane-like structures, known as anchoring plaques. Molecular cloning of the cutaneous BMZ components has allowed elucidation of the structural features of the proteins which constitute these attachment structures. Specifically, hemidesmosomes have been shown to consist of at least four distinct proteins. The intracellular hemidesmosomal inner plaque is comprised of the 230-kD bullous pemphigoid antigen (BPAG1), and plectin, a high-molecular weight cytomatrix protein, encoded by the corresponding gene, PLEC1. The transmembrane component of the hemidesmosomes consists of the 180-kD bullous pemphigoid antigen (BPAG2), a collagenous protein also known as type XVII collagen (COL17A1), as well as of the basal keratinocyte-specific integrin alpha 6 beta 4. The anchoring filaments consist predominantly of laminin 5 with three constitutive subunit polypeptides, the alpha 3, beta 3 and gamma 2 chains, which is associated with laminin 6 with the chain composition alpha 3, beta 1 and gamma 1. Also associated with anchoring filaments is a novel protein, ladinin, which serves as autoantigen in the linear IgA disease, and the corresponding gene, LAD1, has been mapped to human chromosome 1. Finally, the major, if not the exclusive, component of anchoring fibrils is type VII collagen, encoded by the gene (COL7A1) which consists of 118 distinct exons, the largest number of exons in any gene published thus far. Collectively, the cutaneous basement membrane zone is a complex continuum of macromolecules which form a network providing the stable association of the epidermis to the underlying dermis. Thus, genetic lesions resulting in abnormalities in any part of this network could result in a blistering skin disease, such as epidermolysis bullosa.

Antigens, CD↗

PubMed1996

Involvement of the AP-1 site within the 5'-flanking region of the stromelysin-1 gene in induction of the gene expression by UVA irradiation.

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Adolescent↗

PubMed1996

Long-term sun exposure alters the collagen of the papillary dermis. Comparison of sun-protected and photoaged skin by northern analysis, immunohistochemical staining, and confocal laser scanning microscopy.

BACKGROUND: Long-term solar irradiation produces both morphologic and functional changes in affected skin. Because collagen is the major structural component of skin, any alteration in its production or degradation could have profound effects on cutaneous functional integrity. OBJECTIVE: Our purpose was to investigate alterations in the production and morphology of collagen fibers brought about by long-term sun exposure. METHODS: We compared collagen and collagenase gene expression and collagen immunohistochemical staining and used confocal laser scanning microscopy for morphologic examination of dermal collagen fibers in photodamaged compared with sun-protected skin from the same persons. RESULTS: Despite a large increase in elastin messenger RNA in sun-damaged skin, collagen and collagenase gene expression remained essentially unchanged. However, striking alterations in the papillary dermis of photoaged skin were found, which revealed large, abnormally clumped elastic fibers and deformed collagen fibers of various diameters, replacing the normal architecture of the papillary dermis. CONCLUSION: Our data provide evidence for normal collagen gene expression in sun-damaged skin and suggest that degradation and remodeling of collagen take place in the papillary dermis accompanied by deposition of other matrix components, predominantly abnormal elastic fibers.

Blotting, Northern↗

PubMed1996

A molecular defect in loricrin, the major component of the cornified cell envelope, underlies Vohwinkel's syndrome.

Terminal keratinocyte differentiation involves coordinated expression of several functionally interdependent genes, many of which have been mapped to the epidermal differentiation complex (EDC) on chromosome 1q21. We have identified linkage of Vohwinkel's syndrome in an extended pedigree to markers flanking the EDC region with a maximum multipoint lod score of 14.3. Sequencing of the loricrin gene revealed an insertion that shifts the translation frame of the C-terminal Gly- and Gln/Lys-rich domains, and is likely to impair cornification. Our findings provide the first evidence for a defect in an EDC gene in human disease, and disclose novel insights into perturbations of cornified cell envelope formation.

Amino Acid Sequence↗

PubMed1996

Plectin deficiency results in muscular dystrophy with epidermolysis bullosa.

We report that mutation in the gene for plectin, a cytoskeleton-membrane anchorage protein, is a cause of autosomal recessive muscular dystrophy associated with skin blistering (epidermolysis bullosa simplex). The evidence comes from absence of plectin by antibody staining in affected individuals from four families, supportive genetic analysis (localization of the human plectin gene to chromosome 8q24.13-qter and evidence for disease segregation with markers in this region) and finally the identification of a homozygous frameshift mutation detected in plectin cDNA. Absence of the large multifunctional cytoskeleton protein plectin can simultaneously account for structural failure in both muscle and skin.

Amino Acid Sequence↗

PubMed1996

Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy.

In a distinct autosomal recessive variant of epidermolysis bullosa, EB-MD, life-long skin blistering is associated with late-onset muscular dystrophy of unknown etiology. Electron microscopy of these patients' skin suggests that tissue separation occurs intracellularly at the level of the hemidesmosomal inner plaque, which contains plectin, a high molecular weight cytoskeletal associated protein, also expressed in the sarcolemma of the muscle. In this study, we report two patients with EB-MD, each with a homozygous deletion mutation in the plectin gene, PLEC1. In the first case, the proband and her similarly affected sister had a homozygous 9 bp deletion mutation, designated as 2719de19, which resulted in elimination of three amino acids, QEA, in a sequence of 23 amino acids entirely conserved between the mouse and human sequences. The proband in the second family demonstrated a single nucleotide deletion at position 5866, designated as 5866delC, which resulted in frameshift and a premature termination codon for translation 16 bp downstream from the site of deletion. The absence of plectin in the hemidesmosomes, as reflected by negative immunofluorescence with an anti-plectin antibody (HD-1), associated with fragility of basal keratinocytes, implicates plectin as critical for binding of intermediate keratin filament network to hemidesmosomal complexes. The function of plectin as a putative attachment protein also in the muscle would explain the clinical phenotype consisting of cutaneous fragility and muscular dystrophy in EB-MD.

Animals↗