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Keratinocyte-specific knockout mice models via Cre–loxP recombination system

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Abstract

Purpose of review

The Cre recombinase/loxP (Cre/loxP) system has emerged as a useful tool in genetic manipulations. Generally, any DNA sequence of interest can be deleted when flanked with loxP sites. The conditional (timely or spatially controlled) expression of Cre recombinase enables to determine, where (e.g. in which cell type or tissue) and when (at which time of life or of developmental stage of cells/tissues) the deletion of the floxed DNA sequence should occur. Therefore, two mouse lines are usually needed for conditional site-specific genome modification. This review aims to provide a general overview of the Cre/loxP system, elaborate on the different keratinocyte specific knockout mice used to study gene function in keratinocytes, and finally demonstrate the generation of a conditional knockout mice.

Recent findings

Knockout mice have been efficient and powerful approach to understand the functions of specific genes in development and physiological homeostasis. However, deletion of the specific genes which are concerned in stages of development induces to embryonic lethality. To overcome this obstacle, Cre/loxP system has been used to delete a gene in a specific organ or tissue, or at a specific embryonic developmental stage. Conditional knockout mice have allowed extensive research of the epidermis and helped elucidate roles of many gene functions in keratinocytes.

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References

  • Abremski K, Hoess R (1984) Bacteriophage P1 site-specific recombination. Purification and properties of the Cre recombinase protein. J Biol Chem 259:1509–1514

    Article  CAS  PubMed  Google Scholar 

  • Azarova AM et al (2007) Roles of DNA topoisomerase II isozymes in chemotherapy and secondary malignancies. Proc Natl Acad Sci USA 104:11014–11019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bersell K et al (2013) Moderate and high amounts of tamoxifen in alphaMHC-MerCreMer mice induce a DNA damage response, leading to heart failure and death. Dis Model Mech 6:1459–1469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bin BH et al (2017) Requirement of zinc transporter ZIP10 for epidermal development: implication of the ZIP10-p63 axis in epithelial homeostasis. Proc Natl Acad Sci USA 114:12243–12248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boeuf H et al (1997) Leukemia inhibitory factor-dependent transcriptional activation in embryonic stem cells. J Cell Biol 138:1207–1217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bojovic B, Ho HY, Wu J, Crowe DL (2013) Stem cell expansion during carcinogenesis in stem cell-depleted conditional telomeric repeat factor 2 null mutant mice. Oncogene 32:5156–5166

    Article  CAS  PubMed  Google Scholar 

  • Brakebusch C et al (2000) Skin and hair follicle integrity is crucially dependent on beta 1 integrin expression on keratinocytes. EMBO J 19:3990–4003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Byrne C, Fuchs E (1993) Probing keratinocyte and differentiation specificity of the human K5 promoter in vitro and in transgenic mice. Mol Cell Biol 13:3176–3190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Byrne C, Tainsky M, Fuchs E (1994) Programming gene expression in developing epidermis. Development 120:2369–2383

    CAS  PubMed  Google Scholar 

  • Calleja C et al (2006) Genetic and pharmacological evidence that a retinoic acid cannot be the RXR-activating ligand in mouse epidermis keratinocytes. Genes Dev 20:1525–1538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cang Y et al (2007) DDB1 is essential for genomic stability in developing epidermis. Proc Natl Acad Sci USA 104:2733–2737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen J, Den Z, Koch PJ (2008) Loss of desmocollin 3 in mice leads to epidermal blistering. J Cell Sci 121:2844–2849

    Article  CAS  PubMed  Google Scholar 

  • Dainichi T et al (2016) PDK1 is a regulator of epidermal differentiation that activates and organizes asymmetric cell division. Cell Rep 15:1615–1623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Darnell JE Jr (1997) STATs and gene regulation. Science 277:1630–1635

    Article  CAS  PubMed  Google Scholar 

  • Dassule HR et al (2000) Sonic hedgehog regulates growth and morphogenesis of the tooth. Development 127:4775–4785

    CAS  PubMed  Google Scholar 

  • Dauber KL et al (2016) Dissecting the roles of polycomb repressive complex 2 subunits in the control of skin development. J Invest Dermatol 136:1647–1655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Driskell I et al (2012) The histone methyltransferase Setd8 acts in concert with c-Myc and is required to maintain skin. EMBO J 31:616–629

    Article  CAS  PubMed  Google Scholar 

  • Fleger-Weckmann A et al (2016) Deletion of the epidermis derived laminin gamma1 chain leads to defects in the regulation of late hair morphogenesis. Matrix Biol 56:42–56

    Article  CAS  PubMed  Google Scholar 

  • Franzke CW et al (2012) Epidermal ADAM17 maintains the skin barrier by regulating EGFR ligand-dependent terminal keratinocyte differentiation. J Exp Med 209:1105–1119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fuchs E (1991) Keratin genes, epidermal differentiation and animal models for the study of human skin diseases. Biochem Soc Trans 19:1112–1115

    Article  CAS  PubMed  Google Scholar 

  • Gossen M, Bujard H (1992) Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci USA 89:5547–5551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gu H, Zou YR, Rajewsky K (1993) Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targeting. Cell 73:1155–1164

    Article  CAS  PubMed  Google Scholar 

  • Hall B, Limaye A, Kulkarni AB (2009) Overview: generation of gene knockout mice. Curr Protoc Cell Biol 19(12):11–17

    Google Scholar 

  • Hayashi S, McMahon AP (2002) Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: a tool for temporally regulated gene activation/inactivation in the mouse. Dev Biol 244:305–318

    Article  CAS  PubMed  Google Scholar 

  • Heinrich PC et al (1998) Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J 334(Pt 2):297–314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hillmer EJ, Zhang H, Li HS, Watowich SS (2016) STAT3 signaling in immunity. Cytokine Growth Factor Rev 31:1–15

    Article  PubMed  PubMed Central  Google Scholar 

  • Huelsken J et al (2001) beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell 105:533–545

    Article  CAS  PubMed  Google Scholar 

  • Indra AK et al (1999) Temporally-controlled site-specific mutagenesis in the basal layer of the epidermis: comparison of the recombinase activity of the tamoxifen-inducible Cre-ER(T) and Cre-ER(T2) recombinases. Nucleic Acids Res 27:4324–4327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jackson BW et al (1981) Formation of cytoskeletal elements during mouse embryogenesis. II. Epithelial differentiation and intermediate-sized filaments in early postimplantation embryos. Differentiation 20:203–216

    Article  CAS  PubMed  Google Scholar 

  • Janbandhu VC, Moik D, Fassler R (2014) Cre recombinase induces DNA damage and tetraploidy in the absence of loxP sites. Cell Cycle 13:462–470

    Article  CAS  PubMed  Google Scholar 

  • Kanemaru K et al (2012) Epidermal phospholipase Cdelta1 regulates granulocyte counts and systemic interleukin-17 levels in mice. Nat Commun 3:963

    Article  PubMed  CAS  Google Scholar 

  • Kanemaru K et al (2017) Phospholipase Cdelta1 regulates p38 MAPK activity and skin barrier integrity. Cell Death Differ 24:1079–1090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim Y, Zheng Y (2013) Generation and characterization of a conditional deletion allele for Lmna in mice. Biochem Biophys Res Commun 440:8–13

    Article  CAS  PubMed  Google Scholar 

  • Kim H, Kim M, Im SK, Fang S (2018) Mouse Cre-LoxP system: general principles to determine tissue-specific roles of target genes. Lab Anim Res 34:147–159

    Article  PubMed  PubMed Central  Google Scholar 

  • Kistner A et al (1996) Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. Proc Natl Acad Sci USA 93:10933–10938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kopan R, Fuchs E (1989) A new look into an old problem: keratins as tools to investigate determination, morphogenesis, and differentiation in skin. Genes Dev 3:1–15

    Article  CAS  PubMed  Google Scholar 

  • Kos CH (2004) Cre/loxP system for generating tissue-specific knockout mouse models. Nutr Rev 62:243–246

    PubMed  Google Scholar 

  • Lee DW et al (2008) Essential role of cyclin-G-associated kinase (Auxilin-2) in developing and mature mice. Mol Biol Cell 19:2766–2776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee R et al (2010) Genetic studies on the functional relevance of the protein prenyltransferases in skin keratinocytes. Hum Mol Genet 19:1603–1617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levy DE, Lee CK (2002) What does Stat3 do? J Clin Invest 109:1143–1148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li M et al (2001) RXR-alpha ablation in skin keratinocytes results in alopecia and epidermal alterations. Development 128:675–688

    CAS  PubMed  Google Scholar 

  • Li Y, Choi PS, Casey SC, Felsher DW (2014) Activation of Cre recombinase alone can induce complete tumor regression. PLoS ONE 9:e107589

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liakath-Ali K et al (2018) An evolutionarily conserved ribosome-rescue pathway maintains epidermal homeostasis. Nature 556:376–380

    Article  CAS  PubMed  Google Scholar 

  • Longmate WM et al (2017) Suppression of integrin alpha3beta1 by alpha9beta1 in the epidermis controls the paracrine resolution of wound angiogenesis. J Cell Biol 216:1473–1488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loonstra A et al (2001) Growth inhibition and DNA damage induced by Cre recombinase in mammalian cells. Proc Natl Acad Sci USA 98:9209–9214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuda T et al (1999) STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells. Embo J 18:4261–4269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McLellan MA, Rosenthal NA, Pinto AR (2017) Cre-loxP-mediated recombination: general principles and experimental considerations. Curr Protoc Mouse Biol 7:1–12

    Article  PubMed  Google Scholar 

  • Miao Q et al (2019) SOX11 and SOX4 drive the reactivation of an embryonic gene program during murine wound repair. Nat Commun 10:4042

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Minegishi Y et al (2007) Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 448:1058–1062

    Article  CAS  PubMed  Google Scholar 

  • Minegishi Y et al (2009) Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome. J Exp Med 206:1291–1301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Missan DS, Chittur SV, DiPersio CM (2014) Regulation of fibulin-2 gene expression by integrin alpha3beta1 contributes to the invasive phenotype of transformed keratinocytes. J Invest Dermatol 134:2418–2427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mogensen TH (2013) STAT3 and the Hyper-IgE syndrome: Clinical presentation, genetic origin, pathogenesis, novel findings and remaining uncertainties. Jakstat 2:e23435

    PubMed  PubMed Central  Google Scholar 

  • Moll R et al (1982) The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31:11–24

    Article  CAS  PubMed  Google Scholar 

  • Nagy A (2000) Cre recombinase: the universal reagent for genome tailoring. Genesis 26:99–109

    Article  CAS  PubMed  Google Scholar 

  • Nakagawa S et al (2017) Staphylococcusaureus virulent PSMalpha peptides induce keratinocyte alarmin release to orchestrate IL-17-dependent skin inflammation. Cell Host Microbe 22:667-677 e665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nelson WG, Sun TT (1983) The 50- and 58-kdalton keratin classes as molecular markers for stratified squamous epithelia: cell culture studies. J Cell Biol 97:244–251

    Article  CAS  PubMed  Google Scholar 

  • Niwa H, Burdon T, Chambers I, Smith A (1998) Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3. Genes Dev 12:2048–2060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oda Y et al (2018) Vitamin D receptor is required for proliferation, migration, and differentiation of epidermal stem cells and progeny during cutaneous wound repair. J Invest Dermatol 138:2423–2431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park KC et al (2017) Skin-specific deletion of Mis18alpha impedes proliferation and stratification of epidermal keratinocytes. J Invest Dermatol 137:414–421

    Article  CAS  PubMed  Google Scholar 

  • Pasparakis M et al (2002) TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2. Nature 417:861–866

    Article  CAS  PubMed  Google Scholar 

  • Pearson HB et al (2015) The polarity protein Scrib mediates epidermal development and exerts a tumor suppressive function during skin carcinogenesis. Mol Cancer 14:169

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pedranzini L, Leitch A, Bromberg J (2004) Stat3 is required for the development of skin cancer. J Clin Invest 114:619–622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pinto AR et al (2012) An abundant tissue macrophage population in the adult murine heart with a distinct alternatively-activated macrophage profile. PLoS ONE 7:e36814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pinto AR et al (2014) Age-related changes in tissue macrophages precede cardiac functional impairment. Aging (Albany NY) 6:399–413

    Article  Google Scholar 

  • Ponugoti B et al (2013) FOXO1 promotes wound healing through the up-regulation of TGF-beta1 and prevention of oxidative stress. J Cell Biol 203:327–343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qiang L et al (2017) Autophagy gene ATG7 regulates ultraviolet radiation-induced inflammation and skin tumorigenesis. Autophagy 13:2086–2103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramirez A et al (2004) A keratin K5Cre transgenic line appropriate for tissue-specific or generalized Cre-mediated recombination. Genesis 39:52–57

    Article  CAS  PubMed  Google Scholar 

  • Ramirez-Solis R, Liu P, Bradley A (1995) Chromosome engineering in mice. Nature 378:720–724

    Article  CAS  PubMed  Google Scholar 

  • Rashel M, Alston N, Ghazizadeh S (2014) Protein kinase D1 has a key role in wound healing and skin carcinogenesis. J Invest Dermatol 134:902–909

    Article  CAS  PubMed  Google Scholar 

  • Raz R et al (1999) Essential role of STAT3 for embryonic stem cell pluripotency. Proc Natl Acad Sci USA 96:2846–2851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Riese A et al (2012) Epidermal expression of neuropilin 1 protects murine keratinocytes from UVB-induced apoptosis. PLoS ONE 7:e50944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosenberg MP (1997) Gene knockout and transgenic technologies in risk assessment: the next generation. Mol Carcinog 20:262–274

    Article  CAS  PubMed  Google Scholar 

  • Rossant J, McMahon A (1999) “Cre”-ating mouse mutants-a meeting review on conditional mouse genetics. Genes Dev 13:142–145

    Article  CAS  PubMed  Google Scholar 

  • Ruiz S et al (2003) Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130. Development 130:2341–2353

    Article  CAS  PubMed  Google Scholar 

  • Ruiz S et al (2004) Unique and overlapping functions of pRb and p107 in the control of proliferation and differentiation in epidermis. Development 131:2737–2748

    Article  CAS  PubMed  Google Scholar 

  • Sahu RP, DaSilva SC, Rashid B, Martel KC, Jernigan D, Mehta SR, Mohamed DR, Rezania S, Bradish JR, Armstrong AB, Warren S, Konger RL (2012) Mice lacking epidermal PPARγ exhibit a marked augmentation in photocarcinogenesis associated with increased UVB-induced apoptosis, inflammation and barrier dysfunction. Int J Cancer 131(7):E1055–E1066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sano S, Chan KS, DiGiovanni J (2008) Impact of Stat3 activation upon skin biology: a dichotomy of its role between homeostasis and diseases. J Dermatol Sci 50:1–14

    Article  CAS  PubMed  Google Scholar 

  • Sayedyahossein S, Nini L, Irvine TS, Dagnino L (2012) Essential role of integrin-linked kinase in regulation of phagocytosis in keratinocytes. FASEB J 26:4218–4229

    Article  CAS  PubMed  Google Scholar 

  • Schlegelmilch K et al (2011) Yap1 acts downstream of alpha-catenin to control epidermal proliferation. Cell 144:782–795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schnutgen F et al (2005) Genomewide production of multipurpose alleles for the functional analysis of the mouse genome. Proc Natl Acad Sci USA 102:7221–7226

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Schreiber HA et al (2013) Intestinal monocytes and macrophages are required for T cell polarization in response to Citrobacterrodentium. J Exp Med 210:2025–2039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sheng J, Ruedl C, Karjalainen K (2015) Most tissue-resident macrophages except microglia are derived from fetal hematopoietic stem cells. Immunity 43:382–393

    Article  CAS  PubMed  Google Scholar 

  • Shih MY et al (2009) Retinol esterification by DGAT1 is essential for retinoid homeostasis in murine skin. J Biol Chem 284:4292–4299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simpson CL, Patel DM, Green KJ (2011) Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis. Nat Rev Mol Cell Biol 12:565–580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh P et al (2009) Loss of integrin alpha9beta1 results in defects in proliferation, causing poor re-epithelialization during cutaneous wound healing. J Invest Dermatol 129:217–228

    Article  CAS  PubMed  Google Scholar 

  • Snippert HJ et al (2010) Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell 143:134–144

    Article  CAS  PubMed  Google Scholar 

  • Song AJ, Palmiter RD (2018) Detecting and avoiding problems when using the Cre-lox system. Trends Genet 34:333–340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soukharev S, Miller JL, Sauer B (1999) Segmental genomic replacement in embryonic stem cells by double lox targeting. Nucleic Acids Res 27:e21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki A et al (2003) Keratinocyte-specific Pten deficiency results in epidermal hyperplasia, accelerated hair follicle morphogenesis and tumor formation. Cancer Res 63:674–681

    CAS  PubMed  Google Scholar 

  • Takahashi T et al (2017) Epithelial Fli1 deficiency drives systemic autoimmunity and fibrosis: possible roles in scleroderma. J Exp Med 214:1129–1151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takeda K et al (1997) Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc Natl Acad Sci USA 94:3801–3804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takekoshi T et al (2013) CXCR4 negatively regulates keratinocyte proliferation in IL-23-mediated psoriasiform dermatitis. J Invest Dermatol 133:2530–2537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tarutani M et al (1997) Tissue-specific knockout of the mouse Pig-a gene reveals important roles for GPI-anchored proteins in skin development. Proc Natl Acad Sci USA 94:7400–7405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tarutani M et al (2012) GPHR-dependent functions of the Golgi apparatus are essential for the formation of lamellar granules and the skin barrier. J Invest Dermatol 132:2019–2025

    Article  CAS  PubMed  Google Scholar 

  • Thurlings I et al (2017) Synergistic functions of E2F7 and E2F8 are critical to suppress stress-induced skin cancer. Oncogene 36:829–839

    Article  CAS  PubMed  Google Scholar 

  • Torchia EC et al (2013) Aurora kinase-A deficiency during skin development impairs cell division and stratification. J Invest Dermatol 133:78–86

    Article  CAS  PubMed  Google Scholar 

  • Ustun Y et al (2019) Dual role of laminin511 in regulating melanocyte migration and differentiation. Matrix Biol 80:59–71

    Article  PubMed  CAS  Google Scholar 

  • Uto-Konomi A et al (2012) Dysregulation of suppressor of cytokine signaling 3 in keratinocytes causes skin inflammation mediated by interleukin-20 receptor-related cytokines. PLoS ONE 7:e40343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van der Kammen R et al (2017) Knockout of the Arp2/3 complex in epidermis causes a psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2. Development 144:4588–4603

    Article  PubMed  CAS  Google Scholar 

  • Van Keymeulen A et al (2009) Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis. J Cell Biol 187:91–100

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vasioukhin V, Degenstein L, Wise B, Fuchs E (1999) The magical touch: genome targeting in epidermal stem cells induced by tamoxifen application to mouse skin. Proc Natl Acad Sci USA 96:8551–8556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verdoni AM, Ikeda S, Ikeda A (2010) Serum response factor is essential for the proper development of skin epithelium. Mamm Genome 21:64–76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Z et al (2012) Selective ablation of Ctip2/Bcl11b in epidermal keratinocytes triggers atopic dermatitis-like skin inflammatory responses in adult mice. PLoS ONE 7:e51262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weber S et al (2011) The disintegrin/metalloproteinase Adam10 is essential for epidermal integrity and Notch-mediated signaling. Development 138:495–505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wen Z, Zhong Z, Darnell JE Jr (1995) Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell 82:241–250

    Article  CAS  PubMed  Google Scholar 

  • Wu R et al (2020) Nrf2 in keratinocytes protects against skin fibrosis via regulating epidermal lesion and inflammatory response. Biochem Pharmacol 174:113846

    Article  CAS  PubMed  Google Scholar 

  • Yanagida J et al (2012) Accelerated elimination of ultraviolet-induced DNA damage through apoptosis in CDC25A-deficient skin. Carcinogenesis 33:1754–1761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang XO et al (2007) STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem 282:9358–9363

    Article  CAS  PubMed  Google Scholar 

  • Zhang C et al (2017) FOXO1 deletion in keratinocytes improves diabetic wound healing through MMP9 regulation. Sci Rep 7:10565

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang M et al (2019) Cdc42 deficiency leads to epidermal barrier dysfunction by regulating intercellular junctions and keratinization of epidermal cells during mouse skin development. Theranostics 9:5065–5084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu XJ et al (2014) BMP-FGF signaling axis mediates Wnt-induced epidermal stratification in developing mammalian skin. PLoS Genet 10:e1004687

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT and Future Planning (NRF-2019R1A2B5B01070162).

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  1. Ji Won Son and Jung Jin Shin contributed equally to the work.

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  1. Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology, Korea University College of Medicine, 5-ga, Anam-dong, Seongbuk-gu, Seoul, 136-705, South Korea

    Ji Won Son, Min-Gyu Kim, Jaehyung Kim & Sang Wook Son

  2. Aviation Safety Agency, ROK Air Force, Seoul, Republic of Korea

    Jung Jin Shin

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JWS and JJS participated equally in writing the article, analysis and interpretation. M-GK and JK conducted data collection. SWS served as the scientific advisor suggested the conception and design.

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Correspondence to Sang Wook Son.

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Ji Won Son, Jung Jin Shin, Min-Gyu Kim, Jaehyung Kim and Sang Wook Son declare that they have no conflict of interest.

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Son, J.W., Shin, J.J., Kim, MG. et al. Keratinocyte-specific knockout mice models via Cre–loxP recombination system . Mol. Cell. Toxicol. 17, 15–27 (2021). https://doi.org/10.1007/s13273-020-00115-4

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