The novel zebrafish model pretzel demonstrates a central role for SH3PXD2B in defective collagen remodelling and fibrosis in Frank-Ter Haar syndrome
Frank-Ter Haar syndrome (FTHS, MIM #249420) is a rare skeletal dysplasia within the defective collagen remodelling spectrum (DECORS), which is characterised by craniofacial abnormalities, skeletal malformations and fibrotic soft tissues changes including dermal fibrosis and joint contractures. FTHS...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2021
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| Online Access: | https://hdl.handle.net/10356/146674 |
| _version_ | 1811686937714491392 |
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| author | de Vos, Ivo J. H. M. Wong, Arnette Shi Wei Taslim, Jason Ong, Sheena Li Ming Syder, Nicole C. Goggi, Julian L. Carney, Thomas James van Steensel, Maurice A. M. |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) de Vos, Ivo J. H. M. Wong, Arnette Shi Wei Taslim, Jason Ong, Sheena Li Ming Syder, Nicole C. Goggi, Julian L. Carney, Thomas James van Steensel, Maurice A. M. |
| author_sort | de Vos, Ivo J. H. M. |
| collection | NTU |
| description | Frank-Ter Haar syndrome (FTHS, MIM #249420) is a rare skeletal dysplasia within the defective collagen remodelling spectrum (DECORS), which is characterised by craniofacial abnormalities, skeletal malformations and fibrotic soft tissues changes including dermal fibrosis and joint contractures. FTHS is caused by homozygous or compound heterozygous loss-of-function mutation or deletion of SH3PXD2B (Src homology 3 and Phox homology domain-containing protein 2B; MIM #613293). SH3PXD2B encodes an adaptor protein with the same name, which is required for full functionality of podosomes, specialised membrane structures involved in extracellular matrix (ECM) remodelling. The pathogenesis of DECORS is still incompletely understood and, as a result, therapeutic options are limited. We previously generated an mmp14a/b knockout zebrafish and demonstrated that it primarily mimics the DECORS-related bone abnormalities. Here, we present a novel sh3pxd2b mutant zebrafish, pretzel, which primarily reflects the DECORS-related dermal fibrosis and contractures. In addition to relatively mild skeletal abnormalities, pretzel mutants develop dermal and musculoskeletal fibrosis, contraction of which seems to underlie grotesque deformations that include kyphoscoliosis, abdominal constriction and lateral folding. The discrepancy in phenotypes between mmp14a/b and sh3pxd2b mutants suggests that in fish, as opposed to humans, there are differences in spatiotemporal dependence of ECM remodelling on either sh3pxd2b or mmp14a/b The pretzel model presented here can be used to further delineate the underlying mechanism of the fibrosis observed in DECORS, as well as screening and subsequent development of novel drugs targeting DECORS-related fibrosis. |
| first_indexed | 2024-10-01T05:08:21Z |
| format | Journal Article |
| id | ntu-10356/146674 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:08:21Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1466742023-03-05T16:50:26Z The novel zebrafish model pretzel demonstrates a central role for SH3PXD2B in defective collagen remodelling and fibrosis in Frank-Ter Haar syndrome de Vos, Ivo J. H. M. Wong, Arnette Shi Wei Taslim, Jason Ong, Sheena Li Ming Syder, Nicole C. Goggi, Julian L. Carney, Thomas James van Steensel, Maurice A. M. Lee Kong Chian School of Medicine (LKCMedicine) Skin Research Institute of Singapore, A*STAR Science::Medicine FTHS SH3PXD2B Frank-Ter Haar syndrome (FTHS, MIM #249420) is a rare skeletal dysplasia within the defective collagen remodelling spectrum (DECORS), which is characterised by craniofacial abnormalities, skeletal malformations and fibrotic soft tissues changes including dermal fibrosis and joint contractures. FTHS is caused by homozygous or compound heterozygous loss-of-function mutation or deletion of SH3PXD2B (Src homology 3 and Phox homology domain-containing protein 2B; MIM #613293). SH3PXD2B encodes an adaptor protein with the same name, which is required for full functionality of podosomes, specialised membrane structures involved in extracellular matrix (ECM) remodelling. The pathogenesis of DECORS is still incompletely understood and, as a result, therapeutic options are limited. We previously generated an mmp14a/b knockout zebrafish and demonstrated that it primarily mimics the DECORS-related bone abnormalities. Here, we present a novel sh3pxd2b mutant zebrafish, pretzel, which primarily reflects the DECORS-related dermal fibrosis and contractures. In addition to relatively mild skeletal abnormalities, pretzel mutants develop dermal and musculoskeletal fibrosis, contraction of which seems to underlie grotesque deformations that include kyphoscoliosis, abdominal constriction and lateral folding. The discrepancy in phenotypes between mmp14a/b and sh3pxd2b mutants suggests that in fish, as opposed to humans, there are differences in spatiotemporal dependence of ECM remodelling on either sh3pxd2b or mmp14a/b The pretzel model presented here can be used to further delineate the underlying mechanism of the fibrosis observed in DECORS, as well as screening and subsequent development of novel drugs targeting DECORS-related fibrosis. Agency for Science, Technology and Research (A*STAR) Published version This work was supported by Biomedical Research Council (BMRC) A*STAR for the Skin Research Institute of Singapore (H17/01/a0/004 to M.A.M.v.S.), the Acne and Sebaceous Gland Programme (H17/01/a0/008 to M.A.M.v.S.), and the Agency for Science, Technology and Research (A*STAR Research Attachment Programme to I.J.H.M.d.V.). 2021-03-04T08:08:37Z 2021-03-04T08:08:37Z 2020 Journal Article de Vos, I. J. H. M., Wong, A. S. W., Taslim, J., Ong, S. L. M., Syder, N. C., Goggi, J. L., . . . van Steensel, M. A. M. (2020). The novel zebrafish model pretzel demonstrates a central role for SH3PXD2B in defective collagen remodelling and fibrosis in Frank-Ter Haar syndrome. Biology Open, 9(12), bio054270-. doi:10.1242/BIO.054270 2046-6390 https://hdl.handle.net/10356/146674 10.1242/bio.054270 33234702 12 9 en H17/01/a0/004 Biology Open © 2020 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. application/pdf |
| spellingShingle | Science::Medicine FTHS SH3PXD2B de Vos, Ivo J. H. M. Wong, Arnette Shi Wei Taslim, Jason Ong, Sheena Li Ming Syder, Nicole C. Goggi, Julian L. Carney, Thomas James van Steensel, Maurice A. M. The novel zebrafish model pretzel demonstrates a central role for SH3PXD2B in defective collagen remodelling and fibrosis in Frank-Ter Haar syndrome |
| title | The novel zebrafish model pretzel demonstrates a central role for SH3PXD2B in defective collagen remodelling and fibrosis in Frank-Ter Haar syndrome |
| title_full | The novel zebrafish model pretzel demonstrates a central role for SH3PXD2B in defective collagen remodelling and fibrosis in Frank-Ter Haar syndrome |
| title_fullStr | The novel zebrafish model pretzel demonstrates a central role for SH3PXD2B in defective collagen remodelling and fibrosis in Frank-Ter Haar syndrome |
| title_full_unstemmed | The novel zebrafish model pretzel demonstrates a central role for SH3PXD2B in defective collagen remodelling and fibrosis in Frank-Ter Haar syndrome |
| title_short | The novel zebrafish model pretzel demonstrates a central role for SH3PXD2B in defective collagen remodelling and fibrosis in Frank-Ter Haar syndrome |
| title_sort | novel zebrafish model pretzel demonstrates a central role for sh3pxd2b in defective collagen remodelling and fibrosis in frank ter haar syndrome |
| topic | Science::Medicine FTHS SH3PXD2B |
| url | https://hdl.handle.net/10356/146674 |
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