Disease relevance of KRT9

• The common KRT9 gene mutation in a Japanese patient with epidermolytic palmoplantar keratoderma and knuckle pad-like keratoses [1].
• Keratin 9 gene mutations in epidermolytic palmoplantar keratoderma (EPPK) [2].
• Mutations of keratin 9 in two families with palmoplantar epidermolytic hyperkeratosis [3].
• Verification by quantitative reverse transcriptase-PCR confirmed significantly increased expression of keratin 9 (>100-fold) in nonmetastatic breast tumor cells and of CD70 (fivefold) in metastatic cells [4].
• Furthermore, pure epidermal sheets from nonpalmoplantar skin grafted on the human sole wounds due to burn, injury, and the resection of acral lentiginous melanoma, demonstrated adoption of palmoplantar phenotype and expressed keratin 9 [5].

High impact information on KRT9

• These findings provide further evidence that mutations in keratin genes may cause epidermolysis and hyperkeratosis and that hyperkeratosis of palms and soles may be caused by different mutations in the KRT9 gene [2].
• We have isolated the gene for human type I keratin 9 (KRT9) and localised it to chromosome 17q21 [2].
• However, homozygosity by descent was observed with the polymorphic probes KRT9, KRT10 Ava II, and D17S1787 in both affected children, consistent with a recessive defect in a type I keratin [6].
• Several antibodies to K9, raised against synthetic peptides of human K9, recognized the 64- to 62-kDa protein in the perinuclear ring of the manchette as well as in keratinocytes of the suprabasal layer of the rat and human footpad/sole epidermis in both immunoblotting and immunocytochemical experiments [7].
• An increased level of K9 transcripts was detected in a cDNA library prepared from fractionated round spermatids [7].

Chemical compound and disease context of KRT9

• A novel mutation of a leucine residue in coil 1A of keratin 9 in epidermolytic palmoplantar keratoderma [8].

Biological context of KRT9

• By direct sequencing of polymerase chain reaction products, heterozygous missense mutations in exon 1 of KRT9 were detected in all the families [9].
• Molecular characterization of the body site-specific human epidermal cytokeratin 9: cDNA cloning, amino acid sequence, and tissue specificity of gene expression [10].
• DNA sequence analyses revealed single base changes in sequences encoding the highly conserved 1A rod domain segment of the keratin 9 gene in two of the three families [11].
• Our result illustrates the repertoire of KRT9 mutation underlying the occurrence of EPPK in a Japanese family and is an important contribution to the investigation of the genotype/phenotype correlation [12].
• Keratin 9 point mutation in the pedigree of epidermolytic hereditary palmoplantar keratoderma perturbs keratin intermediate filament network formation [13].

Anatomical context of KRT9

• The other, keratin 9, is a component of the perinuclear ring of the manchette, a microtubular structure developed during the elongation and condensation of the spermatid nucleus [14].
• Mutations in the KRT9 gene, encoding keratin 9 (K9), a cytoskeletal protein expressed exclusively in suprabasal keratinocytes of palmoplantar epidermis, have been reported to cause EPPK [15].
• Results of this study show that rat testis expresses K9 and that this protein is a component the perinuclear ring of the manchette of rat spermatids [7].
• Our report indicates extrinsic keratin 9 regulation by signals from dermal fibroblasts [5].
• Sperm tail abnormalities in mutant mice with neo(r) gene insertion into an intron of the keratin 9 gene [16].

Associations of KRT9 with chemical compounds

• DNA sequencing revealed a novel insertion-deletion mutation in the exon 1 of KRT9, 497delAinsGGCT, resulting in the change of tyrosine(166) to tryptophan and leucine (Y166delinsWL) [17].
• In a three-generation Middle Eastern kindred we found a C to T transition at codon 162 that results in an arginine to tryptophan substitution at position 10 of the 1A alpha-helical domain, thus confirming this codon as a hot spot for mutation in keratin 9 [18].
• This is the first case with an Asn160Ser mutation in a Japanese. The substitution of Ser for Asn at codon 160 of the keratin 9 gene is assumed to be fatal for keratin filament assembly regardless of race or ethnicity [19].
• Mass spectrometry analysis of this protein indicated the presence of a glycine-rich domain homologous to human keratin 9 (K9) [7].
• Direct sequencing of genomic DNA samples obtained from several members of each family established the substitution of a highly conserved arginine by tryptophan (R162W) in the 1A region of the alpha-helical rod domain of keratin 9 [20].

Other interactions of KRT9

• The autosomal dominantly transmitted group is further divided into epidermolytic (EPPK, Voerner) and non-epidermolytic (NEPPK, Unna-Thost) types according to the histopathologic findings [11].

Analytical, diagnostic and therapeutic context of KRT9

• A large number of tissues and cell cultures were examined by PCR of mRNA-derived cDNAs, using CK 9-specific primers [10].
• Using CK 9-specific riboprobes for hybridization on Northern blots of RNAs from various epithelia, a mRNA of about 2.4 kb in length could be identified only in foot sole epidermis, and a weaker cross-hybridization signal was seen in RNA from bovine heel pad epidermis at about 2.0 kb [10].
• By in situ hybridization and immunolocalization we further showed that CK 9 is only expressed in the suprabasal cell layers of this special epidermal tissue [10].
• The nuclease digestion pattern seen on Southern blot analysis of human genomic DNA indicated the existence of a unique CK 9 gene [10].
• METHODS: Denaturing high-performance liquid chromatography (DHPLC), DNA sequencing and allele-specific polymerase chain reaction (AS-PCR) were used to screen exon 1 of the KRT9 gene for sequence variations [17].

References