Experimental modeling of congenital epidermolysis bullosa — a tool for studying the pathogenesis and gene therapy targets of the disease

Cover Page

Cite item

Full Text

Abstract

Epidermolysis bullosa (EB) is a phenotypically and genetically heterogeneous group of hereditary dermatoses characterized by the formation of blisters on the skin and/or mucous membranes with minimal mechanical exposure. The study of the pathogenesis and development of therapeutic strategies for EB present significant challenges. In this regard, experimental animal models of EB, especially using laboratory mice, are important in modern science. Genetically modified lines reproducing key mutations in the corresponding genes (Krt5, Krt14, Plec, Lama3, Lamb3, Lamc2, Col7a1, etc.) successfully mimic phenotypic manifestations characteristic of human forms of EB and allow us to study the stages of the pathological process development, as well as to study the molecular basis of the disease and initiate the development of new effective methods of treatment. The advent of genome editing using CRISPR-Cas9, which allows targeted mutations in genes of interest, has simplified the disease modeling process. Further improvement of models is necessary for effective translation of experimental data into clinical practice.

About the authors

Arfenya E. Karamova

State Research Center of Dermatovenereology and Cosmetology

Email: karamova@cnikvi.ru
ORCID iD: 0000-0003-3805-8489
SPIN-code: 3604-6491

MD, Cand. Sci. (Med.), Assistant Professor

Russian Federation, Moscow

Ekaterina V. Girko

State Research Center of Dermatovenereology and Cosmetology

Email: katrin_45_34@mail.ru
ORCID iD: 0000-0001-7723-8701
SPIN-code: 9506-0978

Junior Research Associate

Russian Federation, Moscow

Kseniya M. Aulova

State Research Center of Dermatovenereology and Cosmetology

Author for correspondence.
Email: aulovaksenia@mail.ru
ORCID iD: 0000-0002-2924-3036
SPIN-code: 8310-7019

Junior Research Associate

Russian Federation, Moscow

Xenia I. Plahova

State Research Center of Dermatovenereology and Cosmetology

Email: plahova_xenia@mail.ru
ORCID iD: 0000-0003-4169-4128
SPIN-code: 7634-5521

MD, Dr. Sci. (Med.), Assistant Professor

Russian Federation, Moscow

References

  1. Natsuga K, Shinkuma S, Hsu CK, Fujita Y, Ishiko A, Tamai K, et al. Current topics in Epidermolysis bullosa: pathophysiology and therapeutic challenges. J Dermatol Sci. 2021;104(3):164–176. doi: 10.1016/j.jdermsci.2021.11.004
  2. Hou PC, Wang HT, Abhee S, Tu WT, McGrath JA, Hsu CK. Investigational treatments for epidermolysis bullosa. Am J Clin Dermatol. 2021;22(6):801–817. doi: 10.1007/s40257-021-00626-3
  3. Bolling MC, Lemmink HH, Jansen GH, Jonkman MF. Mutations in KRT5 and KRT14 cause epidermolysis bullosa simplex in 75% of the patients. Br J Dermatol. 2011;164(3):637–644. doi: 10.1111/j.1365-2133.2010.10146.x
  4. Коталевская Ю.Ю., Степанов В.А. Молекулярно-генетические основы буллезного эпидермолиза. Вавиловский журнал генетики и селекции. 2023;27(1):18–27. [Kotalevskaya YuYu, Stepanov VA. Molecular genetic basis of epidermolysis bullosa. Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journal of Genetics and Breeding. 2023;27(1):18–27. (In Russ.)] doi: 10.18699/VJGB-23-04
  5. Hirsch T, Rothoeft T, Teig N, Bauer JW, Pellegrini G, De Rosa L, et al. Regeneration of the entire human epidermis using transgenic stem cells. Nature. 2017;551(7680):327–332. doi: 10.1038/nature24487
  6. Mariath LM, Santin JT, Schuler-Faccini L, Kiszewski AE. Inherited epidermolysis bullosa: update on the clinical and genetic aspects. An Bras Dermatol. 2020;95(5):551–569. doi: 10.1016/j.abd.2020.05.001
  7. Stefanescu BI, Radaschin DS, Mitrea G, Anghel L, Beznea A, Constantin GB, et al. Epidermolysis Bullosa-A Kindler Syndrome Case Report and Short Literature Review. Clin Pract. 2023;13(4):873–880. doi: 10.3390/clinpract13040079
  8. Кубанов А.А., Карамова А.Э., Чикин В.В., Богданова Е.В., Мончаковская Е.С. Эпидемиология и состояние оказания медицинской помощи больным врожденным буллезным эпидермолизом в Российской Федерации. Вестник РАМН. 2018;73(6):420–430. [Kubanov AA, Karamova AA, Chikin VV, Bogdanova EV, Monchakovskaya ES. Epidemiology and Providing of Healthcare for Patients with Inherited Epidermolysis Bullosa in the Russian Federation. Annals of the Russian Academy of Medical Sciences. 2018;73(6):420–430. (In Russ.)] doi: 10.15690/vramn980
  9. So JY, Fulchand S, Wong CY, Li S, Nazaroff J, Gorell ES, et al. A global, cross-sectional survey of patient-reported outcomes, disease burden, and quality of life in epidermolysis bullosa simplex. Orphanet J Rare Dis. 2022;17(1):270. doi: 10.1186/s13023-022-02433-3
  10. Lane EB, McLean WH. Keratins and skin disorders. J Pathol. 2004;204(4):355–366. doi: 10.1002/path.1643
  11. Peters B, Kirfel J, Büssow H, Vidal M, Magin TM. Complete cytolysis and neonatal lethality in keratin 5 knockout mice reveal its fundamental role in skin integrity and in epidermolysis bullosa simplex. Mol Biol Cell. 2001;12(6):1775–1789. doi: 10.1091/mbc.12.6.1775
  12. Lloyd C, Yu QC, Cheng J, Turksen K, Degenstein L, Hutton E, et al. The basal keratin network of stratified squamous epithelia: defining K15 function in the absence of K14. J Cell Biol. 1995;129(5):1329–1344. doi: 10.1083/jcb.129.5.1329
  13. 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. 1991;64(2):365–380. doi: 10.1016/0092-8674(91)90645-f
  14. Cao T, Longley MA, Wang XJ, Roop DR. An inducible mouse model for epidermolysis bullosa simplex: implications for gene therapy. J Cell Biol. 2001;152(3):651–656. doi: 10.1083/jcb.152.3.651
  15. Lane EB, Rugg EL, Navsaria H, Leigh IM, Heagerty AH, Ishida-Yamamoto A, et al. A mutation in the conserved helix termination peptide of keratin 5 in hereditary skin blistering. Nature. 1992;359(6396):670–673. doi: 10.1038/356244a0
  16. Cole-Strauss A, Yoon K, Xiang Y, Byrne BC, Rice MC, Gryn J, et al. Correction of the mutation responsible for sickle cell anemia by an RNA–DNA oligonucleotide. Science. 1996;273(5280):1386–1389. doi: 10.1126/science.273.5280.1386
  17. Alexeev V, Igoucheva O, Domashenko A, Cotsarelis G, Yoon K. Localized in vivo genotypic and phenotypic correction of the albino mutation in skin by RNA–DNA oligonucleotide. Nat Biotechnol. 2000;18(1):43–47. doi: 10.1038/71901
  18. Bolling MC, Jongbloed JD, Boven LG, Diercks GF, Smith FJ, McLean WH, et al. Plectin mutations underlie epidermolysis bullosa simplex in 8% of patients. J Invest Dermatol. 2014;134(1):273–276. doi: 10.1038/jid.2013.277
  19. Andrä K, Lassmann H, Bittner R, Shorny S, Fässler R, Propst F, et al. Targeted inactivation of plectin reveals essential function in maintaining the integrity of skin, muscle, and heart cytoarchitecture. Genes Dev. 1997;11(23):3143–3156. doi: 10.1101/gad.11.23.3143
  20. Ackerl R, Walko G, Fuchs P, Fischer I, Schmuth M, Wiche G. Conditional targeting of plectin in prenatal and adult mouse stratified epithelia causes keratinocyte fragility and lesional epidermal barrier defects. J Cell Sci. 2007;120(Pt 14):2435–2443. doi: 10.1242/jcs.004481
  21. Aumailley M. Laminins and interaction partners in the architecture of the basement membrane at the dermal-epidermal junction. Exp Dermatol. 2021;30(1):17–24. doi: 10.1111/exd.14239
  22. Has C, Bauer JW, Bodemer C, Bolling MC, Bruckner-Tuderman L, Diem A, et al. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol. 2020;183(4):614–627. doi: 10.1111/bjd.18921
  23. Uitto J, Has C, Vahidnezhad H, Youssefian L, Bruckner-Tuderman L. Molecular pathology of the basement membrane zone in heritable blistering diseases: The paradigm of epidermolysis bullosa. Matrix Biol. 2017;57–58:76–85. doi: 10.1016/j.matbio.2016.07.009
  24. Turcan I, Pasmooij AMG, van den Akker PC, Lemmink H, Halmos GB, Sinke RJ, et al. Heterozygosity for a novel missense mutation in the ITGB4 gene associated with autosomal dominant epidermolysis bullosa. JAMA Dermatol. 2016;152(5):558–562. doi: 10.1001/jamadermatol.2015.5236
  25. Ryan MC, Lee K, Miyashita Y, Carter WG. Targeted disruption of the LAMA3 gene in mice reveals abnormalities in survival and late stage differentiation of epithelial cells. J Cell Biol. 1999;145(6):1309–1323. doi: 10.1083/jcb.145.6.1309
  26. Meng X, Klement JF, Leperi DA, Birk DE, Sasaki T, Timpl R, et al. Targeted inactivation of murine laminin gamma2-chain gene recapitulates human junctional epidermolysis bullosa. J Invest Dermatol. 2003;121(4):720–731. doi: 10.1046/j.1523-1747.2003.12515.x
  27. Kuster JE, Guarnieri MH, Ault JG, Flaherty L, Swiatek PJ. IAP insertion in the murine LamB3 gene results in junctional epidermolysis bullosa. Mamm Genome. 1997;8(9):673–681. doi: 10.1007/s003359900535
  28. Bubier JA, Sproule TJ, Alley LM, Webb CM, Fine JD, Roopenian DC, et al. A mouse model of generalized non-Herlitz junctional epidermolysis bullosa. J Invest Dermatol. 2010;130(7):1819–1828. doi: 10.1038/jid.2010.46
  29. Capt A, Spirito F, Guaguere E, Spadafora A, Ortonne JP, Meneguzzi G. Inherited junctional epidermolysis bullosa in the German Pointer: establishment of a large animal model. J Invest Dermatol. 2005;124(3):530–535. doi: 10.1111/j.0022-202X.2004.23584.x
  30. Capt A, Spirito F, Guyon R, André C, Ortonne JP, Meneguzzi G. Cloning of laminin gamma2 cDNA and chromosome mapping of the genes for the dog adhesion ligand laminin 5. Biochem Biophys Res Commun. 2003;312(4):1256–1265. doi: 10.1016/j.bbrc.2003.11.058
  31. Spirito F, Charlesworth A, Linder K, Ortonne JP, Baird J, Meneguzzi G. Animal models for skin blistering conditions: absence of laminin 5 causes hereditary junctional mechanobullous disease in the Belgian horse. J Invest Dermatol. 2002;119(3):684–691. doi: 10.1046/j.1523-1747.2002.01852.x
  32. Lucky AW, Gorell E. Epidermolysis bullosa with pyloric atresia. In: GeneReviews. Adam MP, Feldman J, Mirzaa GM, et al. (eds) University of Washington, Seattle, Seattle (WA); 1993.
  33. Pereda JM de, Lillo MP, Sonnenberg A. Structural basis of the interaction between integrin alpha6beta4 and plectin at the hemidesmosomes. EMBO J. 2009;28(8):1180–1190. doi: 10.1038/emboj.2009.48
  34. Georges-Labouesse E, Messaddeq N, Yehia G, Cadalbert L, Dierich A, Le Meur M. Absence of integrin alpha 6 leads to epidermolysis bullosa and neonatal death in mice. Nat Genet. 1996;13(3):370–373. doi: 10.1038/ng0796-370
  35. van der Neut R, Krimpenfort P, Calafat J, Niessen CM, Sonnenberg A. Epithelial detachment due to absence of hemidesmosomes in integrin beta 4 null mice. Nat Genet. 1996;13(3):366–369. doi: 10.1038/ng0796-366
  36. Raymond K, Kreft M, Janssen H, Calafat J, Sonnenberg A. Keratinocytes display normal proliferation, survival and differentiation in conditional beta4-integrin knockout mice. J Cell Sci. 2005;118(Pt 5):1045–1060. doi: 10.1242/jcs.01689
  37. Has C, Spartà G, Kiritsi D, Weibel L, Moeller A, Vega-Warner V, et al. Integrin α3 mutations with kidney, lung, and skin disease. N Engl J Med. 2012;366(16):1508–1514. doi: 10.1056/NEJMoa1110813
  38. Kinyó Á, Kovács AL, Degrell P, Kálmán E, Nagy N, Kárpáti S, et al. Homozygous ITGA3 Missense Mutation in Adults in a Family with Syndromic Epidermolysis Bullosa (ILNEB) without Pulmonary Involvement. J Invest Dermatol. 2021;141(11):2752–2756. doi: 10.1016/j.jid.2021.03.029
  39. Colombo EA, Spaccini L, Volpi L, Negri G, Cittaro D, Lazarevic D, et al. Viable phenotype of ILNEB syndrome without nephrotic impairment in siblings heterozygous for unreported integrin alpha3 mutations. Orphanet J Rare Dis. 2016;11(1):136. doi: 10.1186/s13023-016-0514-z
  40. DiPersio CM, Hodivala-Dilke KM, Jaenisch R, Kreidberg JA, Hynes RO. alpha3beta1 Integrin is required for normal development of the epidermal basement membrane. J Cell Biol. 1997;137(3):729–742. doi: 10.1083/jcb.137.3.729
  41. Vaz SO, Dâmaso C, Liu L, Ozoemena L, Mota-Vieira L. Severe phenotype of junctional epidermolysis bullosa generalised intermediate type caused by homozygous COL17A1:c.505C>T (p.Arg169*) mutation. Eur J Dermatol. 2018;28(3):412–413. doi: 10.1684/ejd.2018.3279
  42. Van den Bergh F, Giudice GJ. BP180 (type XVII collagen) and its role in cutaneous biology and disease. Adv Dermatol. 2003;19:37–71.
  43. Franzke CW, Tasanen K, Schumann H, Bruckner-Tuderman L. Collagenous transmembrane proteins: collagen XVII as a prototype. Matrix Biol. 2003;22(4):299–309. doi: 10.1016/s0945-053x(03)00051-9
  44. Koster J, Borradori L, Sonnenberg A. Hemidesmosomes: molecular organization and their importance for cell adhesion and disease. Handb Exp Pharmacol. 2004;165:243–280. doi: 10.1007/978-3-540-68170-0-9
  45. Katoh Y, Sato A, Takahashi N, Nishioka Y, Shimizu-Endo N, Ito T, et al. Junctional Epidermolysis Bullosa in Sprague Dawley Rats Caused by a Frameshift Mutation of Col17a1 Gene. Lab Invest. 2024;104(10):102132. doi: 10.1016/j.labinv.2024.102132
  46. Sproule TJ, Bubier JA, Grandi FC, Sun VZ, Philip VM, McPhee CG, et al. Molecular identification of collagen 17a1 as a major genetic modifier of laminin gamma 2 mutation-induced junctional epidermolysis bullosa in mice. PLoS Genet. 2014;10(2):e1004068. doi: 10.1371/journal.pgen.1004068
  47. Parente MG, Chung LC, Ryynänen J, Woodley DT, Wynn KC, Bauer EA, et al. Human type VII collagen: cDNA cloning and chromosomal mapping of the gene. Proc Natl Acad Sci U S A. 1991;88(16):6931–6935. doi: 10.1073/pnas.88.16.6931
  48. Christiano AM, Greenspan DS, Lee S, Uitto J. Cloning of human type VII collagen. Complete primary sequence of the alpha 1(VII) chain and identification of intragenic polymorphisms. J Biol Chem. 1994;269(32):20256–20262.
  49. Кубанов АА, Чикин ВВ, Карамова АЭ. Дистрофический врожденный буллезный эпидермолиз: клинико-генетические корреляции. Вестник дерматологии и венерологии. 2023;99(4):60–83. [Kubanov AA, Chikin VV, Karamova AE. Dystrophic epidermolysis bullosa: genotype-phenotype correlations. Vestnik Dermatologii i Venerologii. 2023;99(4):60–83. (In Russ.)] doi: 10.25208/vdv13281
  50. Fine JD, Bruckner-Tuderman L, Eady RA, Bauer EA, Bauer JW, Has C, et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol. 2014;70(6):1103–1126. doi: 10.1016/j.jaad.2014.01.903
  51. Bruckner-Tuderman L. Dystrophic epidermolysis bullosa: pathogenesis and clinical features. Dermatol Clin. 2010;28(1):107–114. doi: 10.1016/j.det.2009.10.020
  52. Intong LR, Murrell DF. Inherited epidermolysis bullosa: new diagnostic criteria and classification. Clin Dermatol. 2012;30(1):70–77. doi: 10.1016/j.clindermatol.2011.03.012
  53. Fine JD, Mellerio JE. Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part I. Epithelial associated tissues. J Am Acad Dermatol. 2009;61(3):367–384. doi: 10.1016/j.jaad.2009.03.052
  54. Fine JD, Mellerio JE. Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part II. Other organs. J Am Acad Dermatol. 2009;61(3):387–402. doi: 10.1016/j.jaad.2009.03.053
  55. Heinonen S, Männikkö M, Klement JF, Whitaker-Menezes D, Murphy GF, Uitto J. Targeted inactivation of the type VII collagen gene (Col7a1) in mice results in severe blistering phenotype: a model for recessive dystrophic epidermolysis bullosa. J Cell Sci. 1999;112(Pt 21):3641–3648. doi: 10.1242/jcs.112.21.3641
  56. Fritsch A, Loeckermann S, Kern JS, Braun A, Bösl MR, Bley TA, et al. A hypomorphic mouse model of dystrophic epidermolysis bullosa reveals mechanisms of disease and response to fibroblast therapy. J Clin Invest. 2008;118(5):1669–1679. doi: 10.1172/JCI34292
  57. Hong SA, Kim SE, Lee AY, Hwang GH, Kim JH, Iwata H, et al. Therapeutic base editing and prime editing of COL7A1 mutations in recessive dystrophic epidermolysis bullosa. Mol Ther. 2022;30(8):2664–2679. doi: 10.1016/j.ymthe.2022.06.005
  58. Takaki S, Shimbo T, Ikegami K, Kitayama T, Yamamoto Y, Yamazaki S, et al. Generation of a recessive dystrophic epidermolysis bullosa mouse model with patient-derived compound heterozygous mutations. Lab Invest. 2022;102(6):574–580. doi: 10.1038/s41374-022-00735-5
  59. Alipour F, Ahmadraji M, Yektadoost E, Mohammadi P, Baharvand H, Basiri M. CRISPR/Cas9-Mediated Generation of COL7A1-Deficient Keratinocyte Model of Recessive Dystrophic Epidermolysis Bullosa. Cell J. 2023;25(10):665–673. doi: 10.22074/cellj.2023.1989321.1225
  60. García M, Bonafont J, Martínez-Palacios J, Xu R, Turchiano G, Svensson S, et al. Preclinical model for phenotypic correction of dystrophic epidermolysis bullosa by in vivo CRISPR-Cas9 delivery using adenoviral vectors. Mol Ther Methods Clin Dev. 2022;27:96–108. doi: 10.1016/j.omtm.2022.09.005
  61. Webber BR, O’Connor KT, McElmurry RT, Durgin EN, Eide CR, Lees CJ, et al. Rapid generation of Col7a1–/– mouse model of recessive dystrophic epidermolysis bullosa and partial rescue via immunosuppressive dermal mesenchymal stem cells. Lab Invest. 2017;97(10):1218–1224. doi: 10.1038/labinvest.2017.85
  62. Stone W, Strege C, Miller W, Geurts AM, Grzybowski M, Riddle M, et al. Creation and characterization of novel rat model for recessive dystrophic epidermolysis bullosa: Frameshift mutation of the Col7a1 gene leads to severe blistered phenotype. PLoS One. 2024;19(5):e0302991. doi: 10.1371/journal.pone.0302991
  63. Chung HJ, Uitto J. Type VII collagen: the anchoring fibril protein at fault in dystrophic epidermolysis bullosa. Dermatol Clin. 2010;28(1):93– 105. doi: 10.1016/j.det.2009.10.011
  64. Nyström A, Buttgereit J, Bader M, Shmidt T, Ozcelik C, Hausser I, et al. Rat model for dominant dystrophic epidermolysis bullosa: glycine substitution reduces collagen VII stability and shows gene-dosage effect. PLoS One. 2013;8(5):e64243. doi: 10.1371/journal.pone.0064243
  65. Nishida A, Kataoka N, Takeshima Y, Yagi M, Awano H, Ota M, et al. Chemical treatment enhances skipping of a mutated exon in the dystrophin gene. Nat Commun. 2011;2:308. doi: 10.1038/ncomms1306
  66. Goto M, Sawamura D, Nishie W, Sakai K, McMillan JR, Akiyama M, et al. Targeted skipping of a single exon harboring a premature termination codon mutation: implications and potential for gene correction therapy for selective dystrophic epidermolysis bullosa patients. J Invest Dermatol. 2006;126(12):2614–2620. doi: 10.1038/sj.jid.5700435
  67. Smith BRC, Nyström A, Nowell CJ, Hausser I, Gretzmeier C, Robertson SJ, et al. Mouse models for dominant dystrophic epidermolysis bullosa carrying common human point mutations recapitulate the human disease. Dis Model Mech. 2021;14(6):dmm048082. doi: 10.1242/dmm.048082
  68. Youssefian L, Vahidnezhad H, Uitto J. Kindler syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al. (eds) Gene Reviews. Seattle, Seattle (WA): University of Washington; 1993.
  69. Krishna CV, Parmar NV, Has C. Kindler syndrome with severe mucosal involvement in childhood. Clin Exp Dermatol. 2014;39(3):340–343. doi: 10.1111/ced.12293
  70. Krämer S, Hillebrecht AL, Wang Y, Badea MA, Barrios JI, Danescu S, et al. Orofacial Anomalies in Kindler Epidermolysis Bullosa. JAMA Dermatol. 2024;160(5):544–549. doi: 10.1001/jamadermatol.2024.0065
  71. El Hachem M, Diociaiuti A, Proto V, Fortugno P, Zambruno G, Castiglia D, et al. Kindler syndrome with severe mucosal involvement in a large Palestinian pedigree. Eur J Dermatol. 2015;25(1):14–19. doi: 10.1684/ejd.2014.2457
  72. Wiebe CB, Penagos H, Luong N, Slots J, Epstein E Jr, Siegel D, et al. Clinical and microbiologic study of periodontitis associated with Kindler syndrome. J Periodontol. 2003;74(1):25–31. doi: 10.1902/jop.2003.74.1.25
  73. Zhang X, Luo S, Wu J, Zhang L, Wang WH, Degan S, et al. KIND1 Loss Sensitizes Keratinocytes to UV-Induced Inflammatory Response and DNA Damage. J Invest Dermatol. 2017;137(2):475–483. doi: 10.1016/j.jid.2016.09.023
  74. Rognoni E, Widmaier M, Jakobson M, Ruppert R, Ussar S, Katsougkri D, et al. Kindlin-1 controls Wnt and TGF-β availability to regulate cutaneous stem cell proliferation. Nat Med. 2014;20(4):350–359. doi: 10.1038/nm.3490

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2025 Karamova A.E., Girko E.V., Aulova K.M., Plahova X.I.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».