Cutaneous and Developmental Effects of <i>CARD14</i> Overexpression in Zebrafish
Background: Gain-of-function mutations in <i>CARD14</i> have recently been shown to be involved in the pathogenesis of psoriasis and pityriasis rubra pilaris (PRP). Those mutations were found to activate the NF-kB signaling pathway. Objective: Zebrafish is often used to model human disea...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/10/12/3192 |
| _version_ | 1797461320137703424 |
|---|---|
| author | Avital Baniel Limor Ziv Zohar Ben-Moshe Ofer Sarig Janan Mohamad Alon Peled Gideon Rechavi Yoav Gothilf Eli Sprecher |
| author_facet | Avital Baniel Limor Ziv Zohar Ben-Moshe Ofer Sarig Janan Mohamad Alon Peled Gideon Rechavi Yoav Gothilf Eli Sprecher |
| author_sort | Avital Baniel |
| collection | DOAJ |
| description | Background: Gain-of-function mutations in <i>CARD14</i> have recently been shown to be involved in the pathogenesis of psoriasis and pityriasis rubra pilaris (PRP). Those mutations were found to activate the NF-kB signaling pathway. Objective: Zebrafish is often used to model human diseases in general, and in skin disorders more particularly. In the present study, we aimed to examine the effect of <i>CARD14</i> overexpression in zebrafish with the aim to validate this model for future translational applications. Methods: We used light microscopy, scanning electron microscopy, histological analysis and whole mount in situ hybridization as well as real-time PCR to ascertain the effect of <i>CARD14</i> overexpression in the developing zebrafish. Results: Overexpression of human <i>CARD14</i> had a marked morphological and developmental effect on the embryos. Light microscopy demonstrated a characteristic cutaneous pattern including a granular surface and a spiky pigment pattern. In situ hybridization revealed keratinocytes of uneven size and shape. Scanning electron microscopy showed aberrant production of actin microridges and a rugged keratinocyte cell surface, reminiscent of the human hyperkeratotic phenotype. Developmentally, overexpression of <i>CARD14</i> had a variable effect on anterior-posterior axis symmetry. Similar to what has been observed in humans with psoriasis or PRP, NF-kB expression was higher in <i>CARD14</i>-overexpressing embryos compared to controls. Conclusions: Overexpression of <i>CARD14</i> results in a distinct cutaneous pattern accompanied by hyperactivation of the NF-kB pathway, suggesting that the zebrafish represents a useful system to model <i>CARD14</i>-associated papulosquamous diseases. |
| first_indexed | 2024-03-09T17:18:42Z |
| format | Article |
| id | doaj.art-ed303753e0f64c718a3a5cbadf779228 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T17:18:42Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-ed303753e0f64c718a3a5cbadf7792282023-11-24T13:28:27ZengMDPI AGBiomedicines2227-90592022-12-011012319210.3390/biomedicines10123192Cutaneous and Developmental Effects of <i>CARD14</i> Overexpression in ZebrafishAvital Baniel0Limor Ziv1Zohar Ben-Moshe2Ofer Sarig3Janan Mohamad4Alon Peled5Gideon Rechavi6Yoav Gothilf7Eli Sprecher8Division of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, IsraelCancer Research Center, Sheba Medical Center, Ramat Gan 52620, IsraelDepartment of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel Aviv 6997801, IsraelDivision of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, IsraelDivision of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, IsraelDivision of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, IsraelCancer Research Center, Sheba Medical Center, Ramat Gan 52620, IsraelDepartment of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel Aviv 6997801, IsraelDivision of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, IsraelBackground: Gain-of-function mutations in <i>CARD14</i> have recently been shown to be involved in the pathogenesis of psoriasis and pityriasis rubra pilaris (PRP). Those mutations were found to activate the NF-kB signaling pathway. Objective: Zebrafish is often used to model human diseases in general, and in skin disorders more particularly. In the present study, we aimed to examine the effect of <i>CARD14</i> overexpression in zebrafish with the aim to validate this model for future translational applications. Methods: We used light microscopy, scanning electron microscopy, histological analysis and whole mount in situ hybridization as well as real-time PCR to ascertain the effect of <i>CARD14</i> overexpression in the developing zebrafish. Results: Overexpression of human <i>CARD14</i> had a marked morphological and developmental effect on the embryos. Light microscopy demonstrated a characteristic cutaneous pattern including a granular surface and a spiky pigment pattern. In situ hybridization revealed keratinocytes of uneven size and shape. Scanning electron microscopy showed aberrant production of actin microridges and a rugged keratinocyte cell surface, reminiscent of the human hyperkeratotic phenotype. Developmentally, overexpression of <i>CARD14</i> had a variable effect on anterior-posterior axis symmetry. Similar to what has been observed in humans with psoriasis or PRP, NF-kB expression was higher in <i>CARD14</i>-overexpressing embryos compared to controls. Conclusions: Overexpression of <i>CARD14</i> results in a distinct cutaneous pattern accompanied by hyperactivation of the NF-kB pathway, suggesting that the zebrafish represents a useful system to model <i>CARD14</i>-associated papulosquamous diseases.https://www.mdpi.com/2227-9059/10/12/3192zebrafish<i>CARD14</i>psoriasis |
| spellingShingle | Avital Baniel Limor Ziv Zohar Ben-Moshe Ofer Sarig Janan Mohamad Alon Peled Gideon Rechavi Yoav Gothilf Eli Sprecher Cutaneous and Developmental Effects of <i>CARD14</i> Overexpression in Zebrafish Biomedicines zebrafish <i>CARD14</i> psoriasis |
| title | Cutaneous and Developmental Effects of <i>CARD14</i> Overexpression in Zebrafish |
| title_full | Cutaneous and Developmental Effects of <i>CARD14</i> Overexpression in Zebrafish |
| title_fullStr | Cutaneous and Developmental Effects of <i>CARD14</i> Overexpression in Zebrafish |
| title_full_unstemmed | Cutaneous and Developmental Effects of <i>CARD14</i> Overexpression in Zebrafish |
| title_short | Cutaneous and Developmental Effects of <i>CARD14</i> Overexpression in Zebrafish |
| title_sort | cutaneous and developmental effects of i card14 i overexpression in zebrafish |
| topic | zebrafish <i>CARD14</i> psoriasis |
| url | https://www.mdpi.com/2227-9059/10/12/3192 |
| work_keys_str_mv | AT avitalbaniel cutaneousanddevelopmentaleffectsoficard14ioverexpressioninzebrafish AT limorziv cutaneousanddevelopmentaleffectsoficard14ioverexpressioninzebrafish AT zoharbenmoshe cutaneousanddevelopmentaleffectsoficard14ioverexpressioninzebrafish AT ofersarig cutaneousanddevelopmentaleffectsoficard14ioverexpressioninzebrafish AT jananmohamad cutaneousanddevelopmentaleffectsoficard14ioverexpressioninzebrafish AT alonpeled cutaneousanddevelopmentaleffectsoficard14ioverexpressioninzebrafish AT gideonrechavi cutaneousanddevelopmentaleffectsoficard14ioverexpressioninzebrafish AT yoavgothilf cutaneousanddevelopmentaleffectsoficard14ioverexpressioninzebrafish AT elisprecher cutaneousanddevelopmentaleffectsoficard14ioverexpressioninzebrafish |