Myopia disease mouse models: a missense point mutation (S673G) and a protein-truncating mutation of the Zfp644 mimic human disease phenotype
| Autor: | Peter J. Makovicky, Jiri Lindovsky, Jianguo Zhang, Jan Prochazka, Mingming Shi, Jan Dvorak, Chongyi Jiang, Radislav Sedlacek, Agnieszka Kubik-Zahorodna, Xiao Liu, Silvia Petrezsélyová, Mingyan Fang, Vendula Novosadova, Inken M. Beck, Katarzyna Izabela Szczerkowska, Marcela Palkova, Lingyan Chen, Bjoern Schuster |
|---|---|
| Přispěvatelé: | Sedlacek, Radislav [0000-0002-3352-392X], Apollo - University of Cambridge Repository |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
genetic structures Vision lcsh:Biotechnology Mutant Biology Eye General Biochemistry Genetics and Molecular Biology Mouse model lcsh:Biochemistry 03 medical and health sciences 0302 clinical medicine lcsh:TP248.13-248.65 Genetics Myopia Missense mutation lcsh:QD415-436 Gene Transcription factor lcsh:QH301-705.5 Zinc finger Transcription activator-like effector nuclease Research Point mutation Phenotype eye diseases 030104 developmental biology lcsh:Biology (General) FOS: Biological sciences 030220 oncology & carcinogenesis sense organs Zinc finger 644 |
| Zdroj: | Cell & Bioscience, Vol 9, Iss 1, Pp 1-10 (2019) Cell & Bioscience |
| Popis: | Zinc finger 644 (Zfp644 in mouse, ZNF644 in human) gene is a transcription factor whose mutation S672G is considered a potential genetic factor of inherited high myopia. ZNF644 interacts with G9a/GLP complex, which functions as a H3K9 methyltransferase to silence transcription. In this study, we generated mouse models to unravel the mechanisms leading to symptoms associated with high myopia. Employing TALEN technology, two mice mutants were generated, either with the disease-carrying mutation (Zfp644S673G) or with a truncated form of Zfp644 (Zfp644Δ8). Eye morphology and visual functions were analysed in both mutants, revealing a significant difference in a vitreous chamber depth and lens diameter, however the physiological function of retina was preserved as found under the high-myopia conditions. Our findings prove that ZNF644/Zfp644 is involved in the development of high-myopia, indicating that mutations such as, Zfp644S673G and Zfp644Δ8 are causative for changes connected with the disease. The developed models represent a valuable tool to investigate the molecular basis of myopia pathogenesis and its potential treatment. Electronic supplementary material The online version of this article (10.1186/s13578-019-0280-4) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|