A New Mouse Model for Complete Congenital Stationary Night Blindness Due to Gpr179 Deficiency
| Autor: | Orhan, Elise, Neuillé, Marion, Dias, Miguel de Sousa, Pugliese, Thomas, Michiels, Christelle, Condroyer, Christel, Antonio, Aline, Sahel, José-Alain, Audo, Isabelle, Zeitz, Christina |
|---|---|
| Přispěvatelé: | Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Académie des Sciences, Institut de France, University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), University College of London [London] (UCL), Gestionnaire, Hal Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Académie des Sciences [Paris] |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
retina
QH301-705.5 [SDV]Life Sciences [q-bio] mouse model Article b-wave Receptors G-Protein-Coupled Mice Night Blindness Myopia Animals optomotor responses Biology (General) QD1-999 cCSNB congenital stationary night blindness Mice Knockout Eye Diseases Hereditary Genetic Diseases X-Linked [SDV] Life Sciences [q-bio] Mice Inbred C57BL Chemistry dendritic tip staining Disease Models Animal Phenotype ON-bipolar cells Mutation Female sense organs GPR179 Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, MDPI, 2021, 22 (9), pp.4424. ⟨10.3390/ijms22094424⟩ International Journal of Molecular Sciences, 2021, 22 (9), pp.4424. ⟨10.3390/ijms22094424⟩ International Journal of Molecular Sciences, Vol 22, Iss 4424, p 4424 (2021) Volume 22 Issue 9 |
| ISSN: | 1422-0067 1661-6596 |
| DOI: | 10.3390/ijms22094424⟩ |
| Popis: | Mutations in GPR179 lead to autosomal recessive complete congenital stationary night blindness (cCSNB). This condition represents a signal transmission defect from the photoreceptors to the ON-bipolar cells. To confirm the phenotype, better understand the pathogenic mechanism in vivo, and provide a model for therapeutic approaches, a Gpr179 knock-out mouse model was genetically and functionally characterized. We confirmed that the insertion of a neo/lac Z cassette in intron 1 of Gpr179 disrupts the same gene. Spectral domain optical coherence tomography reveals no obvious retinal structure abnormalities. Gpr179 knock-out mice exhibit a so-called no-b-wave (nob) phenotype with severely reduced b-wave amplitudes in the electroretinogram. Optomotor tests reveal decreased optomotor responses under scotopic conditions. Consistent with the genetic disruption of Gpr179, GPR179 is absent at the dendritic tips of ON-bipolar cells. While proteins of the same signal transmission cascade (GRM6, LRIT3, and TRPM1) are correctly localized, other proteins (RGS7, RGS11, and GNB5) known to regulate GRM6 are absent at the dendritic tips of ON-bipolar cells. These results add a new model of cCSNB, which is important to better understand the role of GPR179, its implication in patients with cCSNB, and its use for the development of therapies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|