Diminished Cone Sensitivity in cpfl3 Mice Is Caused by Defective Transducin Signaling
| العنوان: | Diminished Cone Sensitivity in cpfl3 Mice Is Caused by Defective Transducin Signaling |
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| المؤلفون: | Jeannie Chen, Gordon L. Fain, Natalie S. Chen, Rikard Frederiksen, Alapakkam P. Sampath, Norianne T. Ingram |
| المصدر: | Investigative Ophthalmology & Visual Science |
| بيانات النشر: | The Association for Research in Vision and Ophthalmology, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, genetic structures, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, cones, Retinal Diseases, Retinal Rod Photoreceptor Cells, medicine, Animals, Patch clamp, Transducin, Vision, Ocular, Mice, Knockout, GNAT2, Retina, biology, Chemistry, Gap junction, Phosphodiesterase, Retinal, transduction, Heterotrimeric GTP-Binding Proteins, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Gene Expression Regulation, Rhodopsin, Mutation, biology.protein, Biophysics, Retinal Cone Photoreceptor Cells, Female, sense organs, Visual Neuroscience, 030217 neurology & neurosurgery, Photic Stimulation, Signal Transduction |
| الوصف: | Purpose Cone photoreceptor function loss 3 (Gnat2cpfl3/cpfl3 or cpfl3) is a mouse model commonly used as a functional cones null from a naturally occurring mutation in the α-subunit of cone transducin (Gnat2). We nevertheless detected robust cone-mediated light responses from cpfl3 animals, which we now explore. Methods Recordings were made from whole retina and from identified cones with whole-cell patch clamp in retinal slices. Relative levels of GNAT2 protein and numbers of cones in isolated retinas were compared between cpfl3, rod transducin knockout (Gnat1-/-), cpfl3/Gnat1-/- double mutants, and control C57Bl/6J age-matched mice at 4, 9, and 14 weeks of age. Results Cones from cpfl3 and cpfl3/Gnat1-/- mice 2 to 3 months of age displayed normal dark currents but greatly reduced sensitivity and amplification constants. Responses decayed more slowly than in control (C57Bl/6J) mice, indicating an altered mechanism of inactivation. At dim light intensities rod responses could be recorded from cpfl3 cones, indicating intact rod/cone gap junctions. The cpfl3 and cpfl3/Gnat1-/- mice express two-fold less GNAT2 protein compared with C57 at 4 weeks, and a four-fold decrease by 14 weeks. This is accompanied by a small decrease in the number of cones. Conclusions Cplf3 cones can respond to light with currents of normal amplitude and cannot be assumed to be a Gnat2 null. The decreased sensitivity and amplification rate of cones is not explained by a reduction in GNAT2 protein level, but instead by abnormal interactions of the mutant transducin with rhodopsin and the effector molecule, cGMP phosphodiesterase. |
| اللغة: | English |
| تدمد: | 1552-5783 0146-0404 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::75c30e13e2b24f763b0de10d334efee7 http://europepmc.org/articles/PMC7401474 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....75c30e13e2b24f763b0de10d334efee7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15525783 01460404 |
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