Weekly Intraperitoneal Injection of Tamoxifen in an Inducible In Vivo Model of Junctional Epidermolysis Bullosa Generates Early and Advanced Disease Phenotypes
Junctional epidermolysis bullosa caused by loss-of-function variants in genes encoding the skin basement membrane proteins laminin 332, type XVII collagen, or integrin α6β4 affects patients from birth with severe blistering, eventually leading to scarring and early lethality. In this study, we have...
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Elsevier
2025-03-01
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| Series: | JID Innovations |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667026724000791 |
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| author | Eleri Mai Jones Priya Garcha Monique Aumailley Edel Anne O’Toole Emanuel Rognoni Matthew Caley |
| author_facet | Eleri Mai Jones Priya Garcha Monique Aumailley Edel Anne O’Toole Emanuel Rognoni Matthew Caley |
| author_sort | Eleri Mai Jones |
| collection | DOAJ |
| description | Junctional epidermolysis bullosa caused by loss-of-function variants in genes encoding the skin basement membrane proteins laminin 332, type XVII collagen, or integrin α6β4 affects patients from birth with severe blistering, eventually leading to scarring and early lethality. In this study, we have optimized a previously published junctional epidermolysis bullosa–knockout mouse model with weekly tamoxifen intraperitoneal injections, resulting in a more controllable and severe model. Owing to the titratable dosing, this model now recapitulates both early and advanced stages of the human disease, strengthening its use in therapeutic studies. The gradual loss of laminin-α3 in the skin of the mouse through weekly injections lead to generalized blistering and fibrotic dermal changes in multiple skin sites by week 12 after tamoxifen. Our findings demonstrate the usefulness of optimizing tamoxifen induction in Cre-loxP mouse models of extracellular matrix proteins, an approach that could be applicable to other emerging inducible transgenic disease models to improve their ability to mimic the human disease phenotype. |
| format | Article |
| id | doaj-art-f8b593b097f14e7ca3efbfd91a9fab5e |
| institution | DOAJ |
| issn | 2667-0267 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JID Innovations |
| spelling | doaj-art-f8b593b097f14e7ca3efbfd91a9fab5e2025-08-20T02:57:33ZengElsevierJID Innovations2667-02672025-03-015210033110.1016/j.xjidi.2024.100331Weekly Intraperitoneal Injection of Tamoxifen in an Inducible In Vivo Model of Junctional Epidermolysis Bullosa Generates Early and Advanced Disease PhenotypesEleri Mai Jones0Priya Garcha1Monique Aumailley2Edel Anne O’Toole3Emanuel Rognoni4Matthew Caley5Cell Biology & Cutaneous Research, Blizard Institute, Queen Mary University of London, London, United KingdomCell Biology & Cutaneous Research, Blizard Institute, Queen Mary University of London, London, United KingdomCentre for Biochemistry, Medical Faculty, University of Cologne, Cologne, GermanyCell Biology & Cutaneous Research, Blizard Institute, Queen Mary University of London, London, United KingdomCell Biology & Cutaneous Research, Blizard Institute, Queen Mary University of London, London, United Kingdom; Correspondence: Emanuel Rognoni, Cell Biology & Cutaneous Research, Blizard Institute, Queen Mary University of London, London, United Kingdom.Cell Biology & Cutaneous Research, Blizard Institute, Queen Mary University of London, London, United Kingdom; Matthew Caley, Cell Biology & Cutaneous Research, Blizard Institute, Queen Mary University of London, London, United Kingdom.Junctional epidermolysis bullosa caused by loss-of-function variants in genes encoding the skin basement membrane proteins laminin 332, type XVII collagen, or integrin α6β4 affects patients from birth with severe blistering, eventually leading to scarring and early lethality. In this study, we have optimized a previously published junctional epidermolysis bullosa–knockout mouse model with weekly tamoxifen intraperitoneal injections, resulting in a more controllable and severe model. Owing to the titratable dosing, this model now recapitulates both early and advanced stages of the human disease, strengthening its use in therapeutic studies. The gradual loss of laminin-α3 in the skin of the mouse through weekly injections lead to generalized blistering and fibrotic dermal changes in multiple skin sites by week 12 after tamoxifen. Our findings demonstrate the usefulness of optimizing tamoxifen induction in Cre-loxP mouse models of extracellular matrix proteins, an approach that could be applicable to other emerging inducible transgenic disease models to improve their ability to mimic the human disease phenotype.http://www.sciencedirect.com/science/article/pii/S2667026724000791Inducible transgenic modelJunctional EBLamininSkin inflammation |
| spellingShingle | Eleri Mai Jones Priya Garcha Monique Aumailley Edel Anne O’Toole Emanuel Rognoni Matthew Caley Weekly Intraperitoneal Injection of Tamoxifen in an Inducible In Vivo Model of Junctional Epidermolysis Bullosa Generates Early and Advanced Disease Phenotypes JID Innovations Inducible transgenic model Junctional EB Laminin Skin inflammation |
| title | Weekly Intraperitoneal Injection of Tamoxifen in an Inducible In Vivo Model of Junctional Epidermolysis Bullosa Generates Early and Advanced Disease Phenotypes |
| title_full | Weekly Intraperitoneal Injection of Tamoxifen in an Inducible In Vivo Model of Junctional Epidermolysis Bullosa Generates Early and Advanced Disease Phenotypes |
| title_fullStr | Weekly Intraperitoneal Injection of Tamoxifen in an Inducible In Vivo Model of Junctional Epidermolysis Bullosa Generates Early and Advanced Disease Phenotypes |
| title_full_unstemmed | Weekly Intraperitoneal Injection of Tamoxifen in an Inducible In Vivo Model of Junctional Epidermolysis Bullosa Generates Early and Advanced Disease Phenotypes |
| title_short | Weekly Intraperitoneal Injection of Tamoxifen in an Inducible In Vivo Model of Junctional Epidermolysis Bullosa Generates Early and Advanced Disease Phenotypes |
| title_sort | weekly intraperitoneal injection of tamoxifen in an inducible in vivo model of junctional epidermolysis bullosa generates early and advanced disease phenotypes |
| topic | Inducible transgenic model Junctional EB Laminin Skin inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S2667026724000791 |
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