In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-10-09)
Abstract:
Defects in the cilia gene RPGRIP1 cause Leber congenital amaurosis and cone-rod dystrophy in humans. A form of canine cone-rod dystrophy (cord1) was originally associated with a homozygous insertion in RPGRIP1 ( RPGRIP1 ins/ins ) as the primary disease locus while a homozygous deletion in MAP9 ( MAP9 del/del ) was later identified as a modifier associated with the early onset form. However, we find further variability in cone electroretinograms (ERGs) ranging from normal to absent in an extended RPGRIP1 ins/ins canine colony, irrespective of the MAP9 genotype. Ophthalmoscopically, cone ERG absent RPGRIP1 ins/ins eyes show discolouration of the tapetal fundus with varying onset and disease progression, while sd-OCT reveals atrophic changes. Despite marked changes in cone ERG and retinal morphology, photopic vision-guided behaviour is comparable between normal and cone ERG absent RPGRIP1 ins/ins littermates. Cone morphology of the dogs lacking cone ERG are truncated with shortened outer and inner segments. Immunohistochemically, cone ERG absent RPGRIP1 ins/ins retinas have extensive L/M-opsin mislocalization, lack CNGB3 labelling in the L/M-cones, and lack GC1 in all cones. Our results indicate that cord1 is a multigenic disease in which mutations in neither RPGRIP1 nor MAP9 alone lead to visual deficits, and additional gene(s) contribute to cone-specific functional and morphologic defects.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-017-13112-w
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2017
detail.hit.zdb_id:
2615211-3
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