HUMAN USHER-1B MOUSE SHAKER-1 - THE RETINAL PHENOTYPE DISCREPANCY EXPLAINED BY THE PRESENCE ABSENCE OF MYOSIN-VIIA IN THE PHOTORECEPTOR CELLS/

Usher syndrome type I (USH1) associates congenital deafness, vestibula r dysfunction and progressive retinitis pigmentosa leading to blindnes s, The gene encoding myosin VIIA is responsible for USH1B, Mutations i n the murine orthologous gene lead to the shaker-1 phenotype, which ma nifests cochlear and vestibular dysfunction, without any retinal defec t, To address this phenotypic discrepancy, the expression of myosin VI IA in retinal cells was analyzed in human and mouse during embryonic d evelopment and adult life, In the human embryo, myosin VIIA was presen t first in the pigment epithelium cells, and later in these cells as w ell as in the photoreceptor cells, In the adult human retina, myosin V IIA was present in both cell types, In contrast, in mouse, only pigmen t epithelium cells expressed the protein throughout development and ad ult life, Myosin VIIA was also found to be absent in the photoreceptor cells of other rodents (rat and guinea-pig), whereas these cells expr essed the protein in amphibians, avians and primates, These observatio ns suggest that retinitis pigmentosa of USH1B results from a primary r od and cone defect, The USH1B/shaker-1 paradigm illustrates a species- specific cell pattern of gene expression as a possible cause for the d iscrepancy 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 a s in the synaptic ending region where it is co-localized with the syna ptic vesicles, Therefore, we suggest that myosin VIIA might play a rol e in the trafficking of ribbon-synaptic vesicle complexes and the rene wal processes of the outer photoreceptor disks.