Mucopolysaccharidosis IVA: Current Disease Models and Drawbacks
Mucopolysaccharidosis IVA (MPS IVA) is a rare disorder caused by mutations in the N-acetylgalactosamine-6-sulfate-sulfatase (<i>GALNS</i>) encoding gene. GALNS leads to the lysosomal degradation of the glycosaminoglyccreasans keratan sulfate and chondroitin 6-sulfate. Impaired GALNS enzy...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/22/16148 |
| _version_ | 1797459066305380352 |
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| author | Andrés Felipe Leal Carlos Javier Alméciga-Díaz Shunji Tomatsu |
| author_facet | Andrés Felipe Leal Carlos Javier Alméciga-Díaz Shunji Tomatsu |
| author_sort | Andrés Felipe Leal |
| collection | DOAJ |
| description | Mucopolysaccharidosis IVA (MPS IVA) is a rare disorder caused by mutations in the N-acetylgalactosamine-6-sulfate-sulfatase (<i>GALNS</i>) encoding gene. GALNS leads to the lysosomal degradation of the glycosaminoglyccreasans keratan sulfate and chondroitin 6-sulfate. Impaired GALNS enzymes result in skeletal and non-skeletal complications in patients. For years, the MPS IVA pathogenesis and the assessment of promising drugs have been evaluated using in vitro (primarily fibroblasts) and in vivo (mainly mouse) models. Even though value information has been raised from those studies, these models have several limitations. For instance, chondrocytes have been well recognized as primary cells affected in MPS IVA and responsible for displaying bone development impairment in MPS IVA patients; nonetheless, only a few investigations have used those cells to evaluate basic and applied concepts. Likewise, current animal models are extensively represented by mice lacking GALNS expression; however, it is well known that MPS IVA mice do not recapitulate the skeletal dysplasia observed in humans, making some comparisons difficult. This manuscript reviews the current in vitro and in vivo MPS IVA models and their drawbacks. |
| first_indexed | 2024-03-09T16:46:06Z |
| format | Article |
| id | doaj.art-926aeaab8aab4360b156e005306e2b7a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:46:06Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-926aeaab8aab4360b156e005306e2b7a2023-11-24T14:46:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124221614810.3390/ijms242216148Mucopolysaccharidosis IVA: Current Disease Models and DrawbacksAndrés Felipe Leal0Carlos Javier Alméciga-Díaz1Shunji Tomatsu2Nemours Children’s Health, Wilmington, DE 19803, USAInstitute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogotá 110231, ColombiaNemours Children’s Health, Wilmington, DE 19803, USAMucopolysaccharidosis IVA (MPS IVA) is a rare disorder caused by mutations in the N-acetylgalactosamine-6-sulfate-sulfatase (<i>GALNS</i>) encoding gene. GALNS leads to the lysosomal degradation of the glycosaminoglyccreasans keratan sulfate and chondroitin 6-sulfate. Impaired GALNS enzymes result in skeletal and non-skeletal complications in patients. For years, the MPS IVA pathogenesis and the assessment of promising drugs have been evaluated using in vitro (primarily fibroblasts) and in vivo (mainly mouse) models. Even though value information has been raised from those studies, these models have several limitations. For instance, chondrocytes have been well recognized as primary cells affected in MPS IVA and responsible for displaying bone development impairment in MPS IVA patients; nonetheless, only a few investigations have used those cells to evaluate basic and applied concepts. Likewise, current animal models are extensively represented by mice lacking GALNS expression; however, it is well known that MPS IVA mice do not recapitulate the skeletal dysplasia observed in humans, making some comparisons difficult. This manuscript reviews the current in vitro and in vivo MPS IVA models and their drawbacks.https://www.mdpi.com/1422-0067/24/22/16148chondrocytesfibroblastsmousemucopolysaccharidosis IVArat |
| spellingShingle | Andrés Felipe Leal Carlos Javier Alméciga-Díaz Shunji Tomatsu Mucopolysaccharidosis IVA: Current Disease Models and Drawbacks International Journal of Molecular Sciences chondrocytes fibroblasts mouse mucopolysaccharidosis IVA rat |
| title | Mucopolysaccharidosis IVA: Current Disease Models and Drawbacks |
| title_full | Mucopolysaccharidosis IVA: Current Disease Models and Drawbacks |
| title_fullStr | Mucopolysaccharidosis IVA: Current Disease Models and Drawbacks |
| title_full_unstemmed | Mucopolysaccharidosis IVA: Current Disease Models and Drawbacks |
| title_short | Mucopolysaccharidosis IVA: Current Disease Models and Drawbacks |
| title_sort | mucopolysaccharidosis iva current disease models and drawbacks |
| topic | chondrocytes fibroblasts mouse mucopolysaccharidosis IVA rat |
| url | https://www.mdpi.com/1422-0067/24/22/16148 |
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