caa a22 4500 397573286 CHVBK 20180308164847.0 cr unu---uuuuu 161202e199608 xx s 000 0 eng 10.1093/hmg/5.8.1171 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.8.1171 Human Usher 1B/Mouse shaker-1: The Retinal Phenotype Discrepancy Explained By The Presence/Absence of Myosin VIIA in The Photoreceptor Cells [Elektronische Daten] [Aziz El-Amraoui, Iman Sahly, Serge Picaud, José Sahel, Marc Abitbol, Christine Petit] Usher syndrome type I (USH1) associates severe congenital deafness, vestibular dysfunction and progressive retinitis pigmentosa leading to blindness. The gene encoding myosin VIIA is responsible for USH1B. Mutations in the murine orthologous gene lead to the shaker-1 phenotype, which manifests cochlear and vestibular dysfunction, without any retinal defect. To address this phenotypic discrepancy, the expression of myosin VIIA in retinal cells was analyzed in human and mouse during embryonic development and adult life. In the human embryo, myosin VIIA was present first in the pigment epithelium cells, and later in these cells as well as in the photoreceptor cells. In the adult human retina, myosin VIIA was present in both cell types. In contrast, in mouse, only pigment epithelium cells expressed the protein throughout development and adult life. Myosin VIIA was also found to be absent in the photoreceptor cells of other rodents (rat and guinea-pig), whereas these cells expressed the protein in amphibians, avians and primates. These observations suggest that retinitis pigmentosa of USH1B results from a primary rod and cone defect. The USH1B/shaker-1 paradigm illustrates a species-specific cell pattern of gene expression as a possible cause for the discrepancy between phenotypes involving defective orthologous genes in man and mouse. Interestingly, in the photoreceptor cells, myosin VIIA is mainly localized in the inner and base of outer segments as well as in the synaptic ending region where it is co-localized with the synaptic vesicles. Therefore, we suggest that myosin VIIA might play a role in the trafficking of ribbon-synaptic vesicle complexes and the renewal processes of the outer photoreceptor disks. © 1996 Oxford University Press El-Amraoui Aziz Unité de Génétique Moléculaire Humaine, Centre National de la Recherche Scientifique Unité de Recherche Associée 1968, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France aut Sahly Iman Centre de Recherches Thérapeutiques en Ophthalmologie, Laboratoire d'Embryologie Humaine, Faculté de Médecine Necker-Enfants Malades, Université René Descartes, 156 rue de Vaugirard, 75015 Paris, France aut Picaud Serge Laboratoire de Physiopathologie Rétinienne, INSERM CJF 92-02, Université Louis Pasteur, Clinique Ophtalmologique, CHRU-Hôpital Civil, 1 place de l'Hôpital, 67091 Strasbourg cedex, France aut Sahel José Laboratoire de Physiopathologie Rétinienne, INSERM CJF 92-02, Université Louis Pasteur, Clinique Ophtalmologique, CHRU-Hôpital Civil, 1 place de l'Hôpital, 67091 Strasbourg cedex, France aut Abitbol Marc Centre de Recherches Thérapeutiques en Ophthalmologie, Laboratoire d'Embryologie Humaine, Faculté de Médecine Necker-Enfants Malades, Université René Descartes, 156 rue de Vaugirard, 75015 Paris, France aut Petit Christine Unité de Génétique Moléculaire Humaine, Centre National de la Recherche Scientifique Unité de Recherche Associée 1968, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France aut Human Molecular Genetics Oxford University Press 5/8(1996-08), 1171-1178 0964-6906 5:8<1171 1996 5 hmg https://doi.org/10.1093/hmg/5.8.1171 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.8.1171 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- El-Amraoui Aziz Unité de Génétique Moléculaire Humaine, Centre National de la Recherche Scientifique Unité de Recherche Associée 1968, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France aut NATIONALLICENCE 700 1- Sahly Iman Centre de Recherches Thérapeutiques en Ophthalmologie, Laboratoire d'Embryologie Humaine, Faculté de Médecine Necker-Enfants Malades, Université René Descartes, 156 rue de Vaugirard, 75015 Paris, France aut NATIONALLICENCE 700 1- Picaud Serge Laboratoire de Physiopathologie Rétinienne, INSERM CJF 92-02, Université Louis Pasteur, Clinique Ophtalmologique, CHRU-Hôpital Civil, 1 place de l'Hôpital, 67091 Strasbourg cedex, France aut NATIONALLICENCE 700 1- Sahel José Laboratoire de Physiopathologie Rétinienne, INSERM CJF 92-02, Université Louis Pasteur, Clinique Ophtalmologique, CHRU-Hôpital Civil, 1 place de l'Hôpital, 67091 Strasbourg cedex, France aut NATIONALLICENCE 700 1- Abitbol Marc Centre de Recherches Thérapeutiques en Ophthalmologie, Laboratoire d'Embryologie Humaine, Faculté de Médecine Necker-Enfants Malades, Université René Descartes, 156 rue de Vaugirard, 75015 Paris, France aut NATIONALLICENCE 700 1- Petit Christine Unité de Génétique Moléculaire Humaine, Centre National de la Recherche Scientifique Unité de Recherche Associée 1968, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/8(1996-08), 1171-1178 0964-6906 5:8<1171 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford