Genomes and Genes
Gene Symbol: Flg
Alias: AW107830, filaggrin, LOW QUALITY PROTEIN: filaggrin, fillagrin, keratin intermediate filament-associated protein, profilaggrin
- Okano J, Lichti U, Mamiya S, Aronova M, Zhang G, Yuspa S, et al. Increased retinoic acid levels through ablation of Cyp26b1 determine the processes of embryonic skin barrier formation and peridermal development. J Cell Sci. 2012;125:1827-36 pubmed publisher..b, polypeptide 1 (Cyp26b1), a retinoic-acid-degrading enzyme, results in aberrant epidermal differentiation and filaggrin expression, defective cornified envelopes and skin barrier formation, in conjunction with peridermal retention...
- Scharschmidt T, Man M, Hatano Y, Crumrine D, Gunathilake R, Sundberg J, et al. Filaggrin deficiency confers a paracellular barrier abnormality that reduces inflammatory thresholds to irritants and haptens. J Allergy Clin Immunol. 2009;124:496-506, 506.e1-6 pubmed publisher..flaky-tail mouse, which lacks processed murine filaggrin because of a frameshift mutation in the gene encoding profilaggrin that mimics some mutations in human AD, we assessed whether FLG deficiency provokes a barrier abnormality, ..
- Kawasaki H, Nagao K, Kubo A, Hata T, Shimizu A, Mizuno H, et al. Altered stratum corneum barrier and enhanced percutaneous immune responses in filaggrin-null mice. J Allergy Clin Immunol. 2012;129:1538-46.e6 pubmed publisherLoss-of-function mutations in filaggrin are major predisposing factors for atopic dermatitis...
- Pan Y, Lin M, Tian X, Cheng H, Gridley T, Shen J, et al. gamma-secretase functions through Notch signaling to maintain skin appendages but is not required for their patterning or initial morphogenesis. Dev Cell. 2004;7:731-43 pubmed
- Oyoshi M, Murphy G, Geha R. Filaggrin-deficient mice exhibit TH17-dominated skin inflammation and permissiveness to epicutaneous sensitization with protein antigen. J Allergy Clin Immunol. 2009;124:485-93, 493.e1 pubmed publisherb>Filaggrin is important for skin barrier function and is mutated in 15% to 20% of patients with atopic dermatitis...
- Descargues P, Sil A, Sano Y, Korchynskyi O, Han G, Owens P, et al. IKKalpha is a critical coregulator of a Smad4-independent TGFbeta-Smad2/3 signaling pathway that controls keratinocyte differentiation. Proc Natl Acad Sci U S A. 2008;105:2487-92 pubmed publisher..We suggest that a TGFbeta-Smad2/3-IKKalpha axis is a critical Smad4-independent regulator of keratinocyte proliferation and differentiation. ..
- Okuyama R, Nguyen B, Talora C, Ogawa E, Tommasi di Vignano A, Lioumi M, et al. High commitment of embryonic keratinocytes to terminal differentiation through a Notch1-caspase 3 regulatory mechanism. Dev Cell. 2004;6:551-62 pubmed..Thus, a Notch1-caspase 3 regulatory mechanism underlies the intrinsically high commitment of embryonic keratinocytes to terminal differentiation. ..
- Pearton D, Dale B, Presland R. Functional analysis of the profilaggrin N-terminal peptide: identification of domains that regulate nuclear and cytoplasmic distribution. J Invest Dermatol. 2002;119:661-9 pubmedb>Profilaggrin is expressed in the differentiating granular layer of epidermis and other stratified epithelia, where it forms a major component of cytoplasmic keratohyalin granules...
- Resing K, Thulin C, Whiting K, Al Alawi N, Mostad S. Characterization of profilaggrin endoproteinase 1. A regulated cytoplasmic endoproteinase of epidermis. J Biol Chem. 1995;270:28193-8 pubmedb>Profilaggrin, an insoluble precursor of the intermediate filament-associated protein filaggrin, contains multiple internal repeats (PIRs)...
- Moniaga C, Egawa G, Kawasaki H, Hara Chikuma M, Honda T, Tanizaki H, et al. Flaky tail mouse denotes human atopic dermatitis in the steady state and by topical application with Dermatophagoides pteronyssinus extract. Am J Pathol. 2010;176:2385-93 pubmed publisherThe barrier abnormality, a loss-of-function mutation in the gene encoding filaggrin (FLG), which is linked to the incidence of atopic dermatitis (AD), is a recently discovered but important factor in the pathogenesis of AD...
- Presland R, Boggess D, Lewis S, Hull C, Fleckman P, Sundberg J. Loss of normal profilaggrin and filaggrin in flaky tail (ft/ft) mice: an animal model for the filaggrin-deficient skin disease ichthyosis vulgaris. J Invest Dermatol. 2000;115:1072-81 pubmed..Biochemical analysis demonstrated that ft/ft mice lacked normal high molecular profilaggrin (approximately 500 kDa), and instead expressed a lower molecular weight form of profilaggrin (220 kDa) that is ..
- Koch P, de Viragh P, Scharer E, Bundman D, Longley M, Bickenbach J, et al. Lessons from loricrin-deficient mice: compensatory mechanisms maintaining skin barrier function in the absence of a major cornified envelope protein. J Cell Biol. 2000;151:389-400 pubmed
- Andl T, Reddy S, Gaddapara T, Millar S. WNT signals are required for the initiation of hair follicle development. Dev Cell. 2002;2:643-53 pubmed..This phenotype indicates that activation of WNT signaling in the skin precedes, and is required for, localized expression of regulatory genes and initiation of hair follicle placode formation. ..
- Zhang D, Karunaratne S, Kessler M, Mahony D, Rothnagel J. Characterization of mouse profilaggrin: evidence for nuclear engulfment and translocation of the profilaggrin B-domain during epidermal differentiation. J Invest Dermatol. 2002;119:905-12 pubmed..in granular layer keratinocytes and derived by sequential proteolysis from a polyprotein precursor termed profilaggrin. Depending on the species, each profilaggrin molecule contains between 10 and 20 filaggrin subunits organized ..
- Rothnagel J, Longley M, Bundman D, Naylor S, Lalley P, Jenkins N, et al. Characterization of the mouse loricrin gene: linkage with profilaggrin and the flaky tail and soft coat mutant loci on chromosome 3. Genomics. 1994;23:450-6 pubmed..that is formed beneath the plasma membrane of stratified squamous epithelial cells and is coexpressed with profilaggrin in terminally differentiating epidermal keratinocytes...
- Fallon P, Sasaki T, Sandilands A, Campbell L, Saunders S, Mangan N, et al. A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming. Nat Genet. 2009;41:602-8 pubmed publisherLoss-of-function mutations in the FLG (filaggrin) gene cause the semidominant keratinizing disorder ichthyosis vulgaris and convey major genetic risk for atopic dermatitis (eczema), eczema-associated asthma and other allergic phenotypes...
- Romano R, Ortt K, Birkaya B, Smalley K, Sinha S. An active role of the DeltaN isoform of p63 in regulating basal keratin genes K5 and K14 and directing epidermal cell fate. PLoS ONE. 2009;4:e5623 pubmed publisher..DeltaNp63 is a critical mediator of keratinocyte stratification program and directly regulates the basal keratin genes. ..
- Blanpain C, Lowry W, Pasolli H, Fuchs E. Canonical notch signaling functions as a commitment switch in the epidermal lineage. Genes Dev. 2006;20:3022-35 pubmed
- Smyth I, Hacking D, Hilton A, Mukhamedova N, Meikle P, Ellis S, et al. A mouse model of harlequin ichthyosis delineates a key role for Abca12 in lipid homeostasis. PLoS Genet. 2008;4:e1000192 pubmed publisher..Furthermore, we identify Abca12 as a mediator of Abca1-regulated cellular cholesterol efflux, a finding that may have significant implications for other diseases of lipid metabolism and homeostasis, including atherosclerosis...
- Kaufman C, Zhou P, Pasolli H, Rendl M, Bolotin D, Lim K, et al. GATA-3: an unexpected regulator of cell lineage determination in skin. Genes Dev. 2003;17:2108-22 pubmed..This newfound function for GATA-3 in skin development strengthens the parallels between the differentiation programs governing hair follicle and lymphocyte differentiation. ..
- Ruiz S, Segrelles C, Bravo A, Santos M, Perez P, Leis H, et al. Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130. Development. 2003;130:2341-53 pubmed..These results indicate an essential role for p107 and p130 in the epithelial-mesenchimal interactions. ..
- Cangkrama M, Darido C, Georgy S, Partridge D, Auden A, Srivastava S, et al. Two Ancient Gene Families Are Critical for Maintenance of the Mammalian Skin Barrier in Postnatal Life. J Invest Dermatol. 2016;136:1438-1448 pubmed publisher..These findings define the molecular safeguards for barrier function that accompany the transition from intrauterine to terrestrial life. ..
- O Shaughnessy R, Welti J, Sully K, Byrne C. Akt-dependent Pp2a activity is required for epidermal barrier formation during late embryonic development. Development. 2009;136:3423-31 pubmed publisher..We therefore describe a novel Akt-dependent Pp2a activity that acts at least partly through Jun to affect initial barrier formation during late embryonic epidermal development. ..
- Vasioukhin V, Bowers E, Bauer C, Degenstein L, Fuchs E. Desmoplakin is essential in epidermal sheet formation. Nat Cell Biol. 2001;3:1076-85 pubmed..DP is therefore required for assembly of functional desmosomes, maintaining cytoskeletal architecture and reinforcing membrane attachments essential for stable intercellular adhesion. ..
- Jiang Y, Lu B, Crumrine D, Elias P, Feingold K. IL-6 stimulates but is not essential for stratum corneum formation and permeability barrier development during gestation. Exp Dermatol. 2010;19:e31-6 pubmed publisher..These low IL-6 levels may account, at least in part, for the absence of epidermal abnormalities in IL-6 KO mice. In conclusion, exogenous IL-6 accelerates epidermal ontogenesis, but it is not essential for normal epidermal maturation. ..
- Yu Z, Lin K, Bhandari A, Spencer J, Xu X, Wang N, et al. The Grainyhead-like epithelial transactivator Get-1/Grhl3 regulates epidermal terminal differentiation and interacts functionally with LMO4. Dev Biol. 2006;299:122-36 pubmed..These findings indicate that the Get-1 and LMO4 genes interact functionally to regulate epidermal terminal differentiation. ..
- Pendaries V, Malaisse J, Pellerin L, Le Lamer M, Nachat R, Kezic S, et al. Knockdown of filaggrin in a three-dimensional reconstructed human epidermis impairs keratinocyte differentiation. J Invest Dermatol. 2014;134:2938-2946 pubmed publisher..The expression of filaggrin, a protein thought to have a major role in the function of the epidermis, is downregulated...
- Wakabayashi N, Itoh K, Wakabayashi J, Motohashi H, Noda S, Takahashi S, et al. Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat Genet. 2003;35:238-45 pubmed..Breeding to Nrf2-deficient mice reversed the phenotypic Keap1 deficiencies. These experiments show that Keap1 acts upstream of Nrf2 in the cellular response to oxidative and xenobiotic stress. ..
- Cottle D, Ursino G, Ip S, Jones L, DiTommaso T, Hacking D, et al. Fetal inhibition of inflammation improves disease phenotypes in harlequin ichthyosis. Hum Mol Genet. 2015;24:436-49 pubmed publisher..These studies highlight inflammation as an unexpected contributor to HI disease development in utero, and suggest that inhibiting inflammation may reduce disease severity. ..
- Jamora C, Lee P, Kocieniewski P, Azhar M, Hosokawa R, Chai Y, et al. A signaling pathway involving TGF-beta2 and snail in hair follicle morphogenesis. PLoS Biol. 2005;3:e11 pubmed..This novel signaling pathway further weaves together the web of different morphogens and downstream transcriptional events that guide hair bud formation within the developing skin. ..
- Matsui T, Kinoshita Ida Y, Hayashi Kisumi F, Hata M, Matsubara K, Chiba M, et al. Mouse homologue of skin-specific retroviral-like aspartic protease involved in wrinkle formation. J Biol Chem. 2006;281:27512-25 pubmed..This study provides the first evidence that retroviral-like aspartic protease is functionally important in mammalian tissue organization. ..
- O Shaughnessy R, Welti J, Cooke J, Avilion A, Monks B, Birnbaum M, et al. AKT-dependent HspB1 (Hsp27) activity in epidermal differentiation. J Biol Chem. 2007;282:17297-305 pubmed..A key protein in these processes is filaggrin. We show that one target of Akt in granular keratinocytes is HspB1 (heat shock protein 27)...
- Osorio K, Lilja K, Tumbar T. Runx1 modulates adult hair follicle stem cell emergence and maintenance from distinct embryonic skin compartments. J Cell Biol. 2011;193:235-50 pubmed publisher..Thus, a master regulator of hematopoiesis also controls HFSC emergence and maintenance via modulation of bidirectional cross talking between nascent stem cells and their niche. ..
- Mill P, Lee A, Fukata Y, Tsutsumi R, Fukata M, Keighren M, et al. Palmitoylation regulates epidermal homeostasis and hair follicle differentiation. PLoS Genet. 2009;5:e1000748 pubmed publisher..This study is the first to demonstrate a key role for palmitoylation in regulating developmental signals in mammalian tissue homeostasis. ..
- Laurikkala J, Pispa J, Jung H, Nieminen P, Mikkola M, Wang X, et al. Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar. Development. 2002;129:2541-53 pubmed..In conclusion, we suggest that Eda and Edar are associated with the onset of ectodermal patterning and that ectodysplasin/edar signaling also regulates the morphogenesis of hair follicles. ..
- Chen L, Yang Yen H, Tsai C, Thio C, Chuang H, Yang L, et al. Protein Palmitoylation by ZDHHC13 Protects Skin against Microbial-Driven Dermatitis. J Invest Dermatol. 2017;137:894-904 pubmed publisher..In summary, our study suggests that loss of ZDHHC13 in skin impairs the integrity of multiple barrier functions and leads to a dermatitis lesion in response to microbial encounters. ..
- Sevilla L, Latorre V, Sanchis A, Perez P. Epidermal inactivation of the glucocorticoid receptor triggers skin barrier defects and cutaneous inflammation. J Invest Dermatol. 2013;133:361-70 pubmed publisher..Together, our results show that epidermal loss of GR provokes skin barrier defects and cutaneous inflammation...
- Hanley K, Feingold K, Kömüves L, Elias P, Muglia L, Majzoub J, et al. Glucocorticoid deficiency delays stratum corneum maturation in the fetal mouse. J Invest Dermatol. 1998;111:440-4 pubmed..the expression of structural proteins necessary for cornified envelope formation, involucrin, loricrin, and filaggrin, and the activity of the lipid synthetic enzymes beta-glucocerebrosidase and steroid sulfatase, markers of ..
- Schmidt Ullrich R, Tobin D, Lenhard D, Schneider P, Paus R, Scheidereit C. NF-kappaB transmits Eda A1/EdaR signalling to activate Shh and cyclin D1 expression, and controls post-initiation hair placode down growth. Development. 2006;133:1045-57 pubmed..The strongly decreased number of hair follicles observed in c(IkappaBalphaDeltaN) mice compared with tabby mice, indicates that additional signals, such as TROY, must regulate NF-kappaB activity in specific hair follicle subtypes. ..
- Akinduro O, Sully K, Patel A, Robinson D, Chikh A, McPhail G, et al. Constitutive Autophagy and Nucleophagy during Epidermal Differentiation. J Invest Dermatol. 2016;136:1460-1470 pubmed publisher..Our findings may have implications and improve treatment options for patients with epidermal barrierÂ defects. ..
- Bonnart C, Deraison C, Lacroix M, Uchida Y, Besson C, Robin A, et al. Elastase 2 is expressed in human and mouse epidermis and impairs skin barrier function in Netherton syndrome through filaggrin and lipid misprocessing. J Clin Invest. 2010;120:871-82 pubmed publisher..ELA2 localized to keratohyalin granules, where it was found to directly participate in (pro-)filaggrin processing...
- Sehra S, Yao Y, Howell M, Nguyen E, Kansas G, Leung D, et al. IL-4 regulates skin homeostasis and the predisposition toward allergic skin inflammation. J Immunol. 2010;184:3186-90 pubmed publisher..These data suggest that IL-4 plays an important role in regulating epidermal homeostasis and innate barrier function. ..
- Otsuka A, Doi H, Egawa G, Maekawa A, Fujita T, Nakamizo S, et al. Possible new therapeutic strategy to regulate atopic dermatitis through upregulating filaggrin expression. J Allergy Clin Immunol. 2014;133:139-46.e1-10 pubmed publisherNonsense mutations in filaggrin (FLG) represent a significant genetic factor in the cause of atopic dermatitis (AD)...
- Lueders K, Elliott R, Marenholz I, Mischke D, Dupree M, Hamer D. Genomic organization and mapping of the human and mouse neuronal beta2-nicotinic acetylcholine receptor genes. Mamm Genome. 1999;10:900-5 pubmed..3 with the order of markers cen, FLG, IVL, LOR, CHRNB2, tel...
- Dahlhoff M, Muzumdar S, Schafer M, Schneider M. ERBB2 Is Essential for the Growth of Chemically Induced Skin Tumors in Mice. J Invest Dermatol. 2017;137:921-930 pubmed publisher..Thus, ERBB2 may be a promising target for inhibiting human nonmelanoma skin cancer progression. ..
- Devenport D, Fuchs E. Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles. Nat Cell Biol. 2008;10:1257-68 pubmed publisher..Finally, we provide in vitro evidence that homotypic intracellular interactions of Celsr1 are required to recruit Vangl2 and Fzd6 to sites of cell-cell contact. ..
- Katagiri C, Sato J, Nomura J, Denda M. Changes in environmental humidity affect the water-holding property of the stratum corneum and its free amino acid content, and the expression of filaggrin in the epidermis of hairless mice. J Dermatol Sci. 2003;31:29-35 pubmed..We evaluated the skin surface conductance, amino acid in the stratum corneum, and immunoreactivity of filaggrin of the epidermis of hairless mice kept in different environmental humidity...
- Mailleux A, Overholtzer M, Schmelzle T, Bouillet P, Strasser A, Brugge J. BIM regulates apoptosis during mammary ductal morphogenesis, and its absence reveals alternative cell death mechanisms. Dev Cell. 2007;12:221-34 pubmed..These data provide important mechanistic information on the processes involved in sculpting the mammary gland and demonstrate that BIM is a critical regulator of apoptosis in vivo. ..
- Li C, Guo H, Xu X, Weinberg W, Deng C. Fibroblast growth factor receptor 2 (Fgfr2) plays an important role in eyelid and skin formation and patterning. Dev Dyn. 2001;222:471-83 pubmed..Notably, mutant skin remains thin with decreased hair density after transplantation to wild-type recipients. These data demonstrate an essential role of Fgfr2 in eyelid and skin formation and patterning. ..
- Kiso M, Tanaka S, Saba R, Matsuda S, Shimizu A, Ohyama M, et al. The disruption of Sox21-mediated hair shaft cuticle differentiation causes cyclic alopecia in mice. Proc Natl Acad Sci U S A. 2009;106:9292-7 pubmed publisher..These results indicate that Sox21 is a master regulator of hair shaft cuticle differentiation and shed light on the possible causes of human hair disorders. ..
- Kobayashi T, Glatz M, Horiuchi K, Kawasaki H, Akiyama H, Kaplan D, et al. Dysbiosis and Staphylococcus aureus Colonization Drives Inflammation in Atopic Dermatitis. Immunity. 2015;42:756-66 pubmed publisher..aureus inoculation. These results characterize differential contributions of dysbiotic flora during eczema formation, and highlight the microbiota-host immunity axis as a possible target for future therapeutics in eczematous dermatitis. ..
- Su X, Cho M, Gi Y, Ayanga B, Sherr C, Flores E. Rescue of key features of the p63-null epithelial phenotype by inactivation of Ink4a and Arf. EMBO J. 2009;28:1904-15 pubmed publisher..Thus, in the absence of p63, abnormal upregulation of Ink4a and Arf is incompatible with skin development. ..
- Cox P, Zoghbi H. Sequencing, expression analysis, and mapping of three unique human tropomodulin genes and their mouse orthologs. Genomics. 2000;63:97-107 pubmed..Our mapping efforts revealed new regions of paralogy among chromosomes 1q, 9q, 15q, and 19p. ..
- Bager P, Wohlfahrt J, Thyssen J, Melbye M. Filaggrin genotype and skin diseases independent of atopic dermatitis in childhood. Pediatr Allergy Immunol. 2016;27:162-8 pubmed publisherb>Filaggrin gene (FLG) mutations compromise skin barrier functions and increase risk of atopic dermatitis. We aimed to study effects on other skin diseases using unique data from the Danish registers...
- Hwang M, Kalinin A, Morasso M. The temporal and spatial expression of the novel Ca++-binding proteins, Scarf and Scarf2, during development and epidermal differentiation. Gene Expr Patterns. 2005;5:801-8 pubmed..e. keratin 14 (K14), keratin 1 (K1), loricrin (LOR) and filaggrin (FIL) showed that their expression overlaps K1, an early marker of keratinocyte differentiation...
- Dauber K, Perdigoto C, Valdes V, Santoriello F, Cohen I, Ezhkova E. Dissecting the Roles of Polycomb Repressive Complex 2 Subunits in the Control of Skin Development. J Invest Dermatol. 2016;136:1647-1655 pubmed publisher..The strikingly different roles of PRC2 in the formation of three lineages exemplify the complex outcomes that the lack of PRC2 can have in a somatic stem cell system. ..
- Chakravarti D, Su X, Cho M, Bui N, Coarfa C, Venkatanarayan A, et al. Induced multipotency in adult keratinocytes through down-regulation of ?Np63 or DGCR8. Proc Natl Acad Sci U S A. 2014;111:E572-81 pubmed publisher..Our data reveal a role for ?Np63 in the transcriptional regulation of DGCR8 to reprogram adult somatic cells into multipotent stem cells. ..
- Funato N, Nakamura M, Richardson J, Srivastava D, Yanagisawa H. Tbx1 regulates oral epithelial adhesion and palatal development. Hum Mol Genet. 2012;21:2524-37 pubmed publisher..Our present study reveals new pathogenesis of incomplete and submucous cleft palate during mammalian palatogenesis. ..
- Pichery M, Huchenq A, Sandhoff R, Severino Freire M, Zaafouri S, Opálka L, et al. PNPLA1 defects in patients with autosomal recessive congenital ichthyosis and KO mice sustain PNPLA1 irreplaceable function in epidermal omega-O-acylceramide synthesis and skin permeability barrier. Hum Mol Genet. 2017;26:1787-1800 pubmed publisher..Overall, our data support that PNPLA1/Pnpla1 is a key player in the formation of ?-O-acylceramide, a crucial process for the epidermal permeability barrier function. ..
- Lane P. Two new mutations in linkage group XVI of the house mouse. Flaky tail and varitint-waddler-J. J Hered. 1972;63:135-40 pubmed
- Lee J, Kim T, Yang T, Koo B, Oh S, Lee K, et al. A crucial role of WW45 in developing epithelial tissues in the mouse. EMBO J. 2008;27:1231-42 pubmed publisher..Collectively, these data provide compelling evidence that WW45 is a key mediator of MST1 signalling in the coordinate coupling of proliferation arrest with terminal differentiation for proper epithelial tissue development in mammals. ..
- Georgy S, Cangkrama M, Srivastava S, Partridge D, Auden A, Dworkin S, et al. Identification of a Novel Proto-oncogenic Network in Head and Neck Squamous Cell Carcinoma. J Natl Cancer Inst. 2015;107: pubmed publisher..84 X 10(3), P = .003) and human HNSCC cells. We defined a novel molecular signature in mammalian HNSCC, suggesting new treatment strategies targeting the GRHL3/GSK3B/c-MYC proto-oncogenic network. ..
- Beronja S, Janki P, Heller E, Lien W, Keyes B, Oshimori N, et al. RNAi screens in mice identify physiological regulators of oncogenic growth. Nature. 2013;501:185-90 pubmed publisher..By documenting some oncogenic growth regulators, we pave the way for future investigations of other hits and raise promise for unearthing new targets for cancer therapies. ..
- Sevilla L, Nachat R, Groot K, Klement J, Uitto J, Djian P, et al. Mice deficient in involucrin, envoplakin, and periplakin have a defective epidermal barrier. J Cell Biol. 2007;179:1599-612 pubmed publisher..of proteases is reduced and the protease inhibitor, serpina1b, is highly upregulated, resulting in defective filaggrin processing and delayed degradation of desmoglein 1 and corneodesmosin...
- Sasaki T, Shiohama A, Kubo A, Kawasaki H, Ishida Yamamoto A, Yamada T, et al. A homozygous nonsense mutation in the gene for Tmem79, a component for the lamellar granule secretory system, produces spontaneous eczema in an experimental model of atopic dermatitis. J Allergy Clin Immunol. 2013;132:1111-1120.e4 pubmed publisherFlaky tail (ma/ma Flg(ft/ft)) mice have a frameshift mutation in the filaggrin (Flg(ft)) gene and are widely used as a model of human atopic dermatitis associated with FLG mutations...
- Morasso M, Markova N, Sargent T. Regulation of epidermal differentiation by a Distal-less homeodomain gene. J Cell Biol. 1996;135:1879-87 pubmed..The basal cells of affected mice ceased to proliferate, and expressed the profilaggrin and loricrin genes which are normally transcribed only in the latest stages of epidermal differentiation...
- Makino T, Takaishi M, Morohashi M, Huh N. Hornerin, a novel profilaggrin-like protein and differentiation-specific marker isolated from mouse skin. J Biol Chem. 2001;276:47445-52 pubmed..the granular cells of the epidermis, the hornerin protein was detected in keratohyalin granules together with profilaggrin. Furthermore, Western blot analysis of the mouse skin showed that the hornerin protein was cleaved during the ..
- Chin S, Romano R, Nagarajan P, Sinha S, Garrett Sinha L. Aberrant epidermal differentiation and disrupted ?Np63/Notch regulatory axis in Ets1 transgenic mice. Biol Open. 2013;2:1336-45 pubmed publisher..Given the established tumor suppressive role for Notch signaling in skin tumorigenesis, the demonstrated ability of Ets1 to interfere with this signaling pathway may be important in mediating its pro-tumorigenic activities. ..
- Den Z, Cheng X, Merched Sauvage M, Koch P. Desmocollin 3 is required for pre-implantation development of the mouse embryo. J Cell Sci. 2006;119:482-9 pubmed..Unexpectedly, homozygous mutants show a pre-implantation lethal phenotype. In fact, most mutants die even before mature desmosomes are formed in the embryo, suggesting a new and unexpected role of Dsc3 during early development. ..
- Ingraham C, Kinoshita A, Kondo S, Yang B, Sajan S, Trout K, et al. Abnormal skin, limb and craniofacial morphogenesis in mice deficient for interferon regulatory factor 6 (Irf6). Nat Genet. 2006;38:1335-40 pubmed..Histological and gene expression analyses indicate that the primary defect is in keratinocyte differentiation and proliferation. This study describes a new role for an IRF family member in epidermal development. ..
- Yamamoto K, Miki Y, Sato M, Taketomi Y, Nishito Y, Taya C, et al. The role of group IIF-secreted phospholipase A2 in epidermal homeostasis and hyperplasia. J Exp Med. 2015;212:1901-19 pubmed publisher..Our results highlight PLA2G2F as a previously unrecognized regulator of skin pathophysiology and point to this enzyme as a novel drug target for epidermal-hyperplasic diseases. ..
- Elkenani M, Nyamsuren G, Raju P, Liakath Ali K, Hamdaoui A, Kata A, et al. Pelota Regulates Epidermal Differentiation by Modulating BMP and PI3K/AKT Signaling Pathways. J Invest Dermatol. 2016;136:1664-1671 pubmed publisher..Further analysis indicated that this phenotype is a result of failed processing of profilaggrin into filaggrin monomers, which promotes the formation of a protective epidermal layer...
- Gao X, Copeland N, Gilbert D, Jenkins N, Gridley T. Assignment of the murine Notch2 and Notch3 genes to chromosomes 3 and 17. Genomics. 1998;49:160-1 pubmed
- Nakatsuji T, Chen T, Two A, Chun K, Narala S, Geha R, et al. Staphylococcus aureus Exploits Epidermal Barrier Defects in Atopic Dermatitis to Trigger Cytokine Expression. J Invest Dermatol. 2016;136:2192-2200 pubmed publisher..and in mice but was found to be increased in the skin of cathelicidin knockout and ovalbumin-sensitized filaggrin mutant mice. S...