Genetic and Functional Differences between Duplicated Zebrafish Genes for Human <i>SCN1A</i>
There are currently seven different zebrafish strains that model Dravet Syndrome, a severe childhood form of epilepsy. These models are based on a set of duplicated genes, <i>scn1laa</i> and <i>scn1lab</i>, which are the homologs for human <i>SCN1A</i>. Disrupting...
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MDPI AG
2022-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/3/454 |
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| author | Wout J. Weuring Jos W. Hoekman Kees P. J. Braun Bobby P. C. Koeleman |
| author_facet | Wout J. Weuring Jos W. Hoekman Kees P. J. Braun Bobby P. C. Koeleman |
| author_sort | Wout J. Weuring |
| collection | DOAJ |
| description | There are currently seven different zebrafish strains that model Dravet Syndrome, a severe childhood form of epilepsy. These models are based on a set of duplicated genes, <i>scn1laa</i> and <i>scn1lab</i>, which are the homologs for human <i>SCN1A</i>. Disrupting one of the genes would mimic a heterozygous disease state in humans, as the paralog gene is still present. While this ‘disease-state model’ is widely accepted, there is also evidence that the function of these genes might not be completely the same. By analyzing the functional domains, we discovered several hotspots in the protein that are not conserved, indicating a functional difference. Based on this, we generated <i>scn1Laa</i> knockout zebrafish and compared their phenotype to <i>scn1lab</i> knockouts. The genetic and functional differences we discovered can have implications for the use of zebrafish as a model for Dravet Syndrome. |
| first_indexed | 2024-03-10T00:03:09Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T00:03:09Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-4fe5bd423bb54af689826500e3aca28c2023-11-23T16:12:09ZengMDPI AGCells2073-44092022-01-0111345410.3390/cells11030454Genetic and Functional Differences between Duplicated Zebrafish Genes for Human <i>SCN1A</i>Wout J. Weuring0Jos W. Hoekman1Kees P. J. Braun2Bobby P. C. Koeleman3Department of Genetics, University Medical Center Utrecht, 3584 Utrecht, The NetherlandsDepartment of Genetics, University Medical Center Utrecht, 3584 Utrecht, The NetherlandsDepartment of Neurology & Neurosurgery, University Medical Centre Utrecht, 3584 Utrecht, The NetherlandsDepartment of Genetics, University Medical Center Utrecht, 3584 Utrecht, The NetherlandsThere are currently seven different zebrafish strains that model Dravet Syndrome, a severe childhood form of epilepsy. These models are based on a set of duplicated genes, <i>scn1laa</i> and <i>scn1lab</i>, which are the homologs for human <i>SCN1A</i>. Disrupting one of the genes would mimic a heterozygous disease state in humans, as the paralog gene is still present. While this ‘disease-state model’ is widely accepted, there is also evidence that the function of these genes might not be completely the same. By analyzing the functional domains, we discovered several hotspots in the protein that are not conserved, indicating a functional difference. Based on this, we generated <i>scn1Laa</i> knockout zebrafish and compared their phenotype to <i>scn1lab</i> knockouts. The genetic and functional differences we discovered can have implications for the use of zebrafish as a model for Dravet Syndrome.https://www.mdpi.com/2073-4409/11/3/454Dravet Syndromegenome duplicationSCN1ANav1.1VGSC |
| spellingShingle | Wout J. Weuring Jos W. Hoekman Kees P. J. Braun Bobby P. C. Koeleman Genetic and Functional Differences between Duplicated Zebrafish Genes for Human <i>SCN1A</i> Cells Dravet Syndrome genome duplication SCN1A Nav1.1 VGSC |
| title | Genetic and Functional Differences between Duplicated Zebrafish Genes for Human <i>SCN1A</i> |
| title_full | Genetic and Functional Differences between Duplicated Zebrafish Genes for Human <i>SCN1A</i> |
| title_fullStr | Genetic and Functional Differences between Duplicated Zebrafish Genes for Human <i>SCN1A</i> |
| title_full_unstemmed | Genetic and Functional Differences between Duplicated Zebrafish Genes for Human <i>SCN1A</i> |
| title_short | Genetic and Functional Differences between Duplicated Zebrafish Genes for Human <i>SCN1A</i> |
| title_sort | genetic and functional differences between duplicated zebrafish genes for human i scn1a i |
| topic | Dravet Syndrome genome duplication SCN1A Nav1.1 VGSC |
| url | https://www.mdpi.com/2073-4409/11/3/454 |
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