P02.10.C Cataract and retinal dystrophy inVps13b(Delta Ex3/Delta Ex3)mice
| Autor: | Lhussiez, Vincent, Cesar, Quénol, Dubus, Elisabeth, Simonutti, Manuel, Lizé, Eléonore, Nguyen, Sylvie, Geissler, Audrey, Bouchot, André, Picaud, Serge, Nandrot, Emeline F., Acar, Niyazi, Faivre, Laurence, Thauvin, Christel, Duplomb, Laurence, Da Costa, Romain |
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| Přispěvatelé: | Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | European Society of Human Genetics 53. European Society of Human Genetics (ESHG) Conference 53. European Society of Human Genetics (ESHG) Conference, Jun 2020, Virtual conference, United Kingdom. pp.141-797, ⟨10.1038/s41431-020-00739-z⟩ |
| Popis: | International audience; Cohen syndrome (CS) is a rare genetic disorder due to variation in the VPS13B gene. It is characterized by a wide variety of clinical features that includes a typical facial dysmorphism, hypotonia, neutropenia, microcephaly, intellectual disability and severe visual impairments. In their early childhood, CS patients already suffer from myopia and a retinal dystrophy that affects both peripheral and central vision. In addition, long-term outcome studies showed that cataract reaches a high prevalence in adults with CS in their forties. To understand how VPS13B variants lead to these visual impairments and have the possibility to assess therapeutic approaches, we generated the Vps13bΔEx3/ΔEx3 mouse model. Cataract was almost systematic in 2-month-old animals. Eye fundi appeared normal until cataract development, but OCT, ERG and histological data suggest that rod homeostasis may be affected in the few Vps13bΔEx3/ΔEx3 mice without cataract after 5 months of age. Immunostaining of the lens revealed that cataract formation was associated with the appearance of large vacuoles in the cortical area, epithelial-mesenchymal transition and fibrosis. In later stages, cataracts became hypermature, lens capsules ruptured, and sclerotic nuclear parts dissociated. Altogether, our results show that Vps13b has a function in lens homeostasis in mice and that the Vps13bΔEx3/ΔEx3 mouse line is a useful model to study the pathomechanism leading to CS-related cataract. |
| Databáze: | OpenAIRE |
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