Inhibition of histone deacetylation rescues phenotype in a mouse model of Birk-Barel intellectual disability syndrome
- Mutations in the actively expressed, maternal allele of the imprinted KCNK9 gene cause Birk-Barel intellectual disability syndrome (BBIDS). Using a BBIDS mouse model, we identify here a partial rescue of the BBIDS-like behavioral and neuronal phenotypes mediated via residual expression from the paternal Kcnk9 (Kcnk9pat) allele. We further demonstrate that the second-generation HDAC inhibitor CI-994 induces enhanced expression from the paternally silenced Kcnk9 allele and leads to a full rescue of the behavioral phenotype suggesting CI-994 as a promising molecule for BBIDS therapy. Thus, these findings suggest a potential approach to improve cognitive dysfunction in a mouse model of an imprinting disorder.
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| Author: | Alexis Cooper, Tamer Butto, Niklas Hammer, Somanath Jagannath, Desiree Lucia Fend-Guella, Junaid Akhtar, Konstantin Radyushkin, Florian Lesage, Jennifer Winter, Susanne Strand, Jochen RoeperORCiD, Ulrich Zechner, Susann Schweiger |
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| URN: | urn:nbn:de:hebis:30:3-551103 |
| DOI: | https://doi.org/10.1038/s41467-019-13918-4 |
| ISSN: | 2041-1723 |
| Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/31980599 |
| Parent Title (English): | Nature Communications |
| Publisher: | Nature Publishing Group UK |
| Place of publication: | [London] |
| Document Type: | Article |
| Language: | English |
| Year of Completion: | 2020 |
| Date of first Publication: | 2020/01/24 |
| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
| Release Date: | 2020/07/20 |
| Tag: | Developmental disorders; Epigenetics; Neurodevelopmental disorders |
| Volume: | 11 |
| Issue: | 1, Art. 480 |
| Page Number: | 14 |
| First Page: | 1 |
| Last Page: | 14 |
| Note: | Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| HeBIS-PPN: | 467705445 |
| Institutes: | Medizin / Medizin |
| Angeschlossene und kooperierende Institutionen / Senckenbergische Naturforschende Gesellschaft | |
| Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
| Sammlungen: | Universitätspublikationen |
| Licence (German): |  Creative Commons - Namensnennung 4.0 |
