A Mutation in Syne2 Causes Early Retinal Defects in Photoreceptors, Secondary Neurons, and Müller Glia.
Document Type
Article
Publication Date
6-1-2015
JAX Source
Invest Ophthalmol Vis Sci 2015 Jun; 56(6):3776-87.
Volume
56
Issue
6
First Page
3776
Last Page
3787
ISSN
1552-5783
PMID
26066746
Abstract
PURPOSE: The purpose of this study was to identify the molecular basis and characterize the pathological consequences of a spontaneous mutation named cone photoreceptor function loss 8 (cpfl8) in a mouse model with a significantly reduced cone electroretinography (ERG) response.
METHODS: The chromosomal position for the recessive cpfl8 mutation was determined by DNA pooling and by subsequent genotyping with simple sequence length polymorphic markers in an F2 intercross phenotyped by ERG. Genes within the candidate region of both mutants and controls were directly sequenced and compared. The effects of the mutation were examined in longitudinal studies by light microscopy, marker analysis, transmission electron microscopy, and ERG.
RESULTS: The cpfl8 mutation was mapped to Chromosome 12, and a premature stop codon was identified in the spectrin repeat containing nuclear envelope 2 (Syne2) gene. The reduced cone ERG response was due to a significant reduction in cone photoreceptors. Longitudinal studies of the early postnatal retina indicated that the cone photoreceptors fail to develop properly, rod photoreceptors mislocalize to the inner nuclear layer, and both rods and cones undergo apoptosis prematurely. Moreover, we observed migration defects of secondary neurons and ectopic Müller cell bodies in the outer nuclear layer in early postnatal development.
CONCLUSIONS: SYNE2 is important for normal retinal development. We have determined that not only is photoreceptor nuclear migration affected, but also the positions of Müller glia and secondary neurons are disturbed early in retinal development. The cpfl8 mouse model will serve as an important resource for further examining the role of nuclear scaffolding and migration in the developing retina.
Invest Ophthalmol Vis Sci 2015 Jun; 56(6):3776-87.
Recommended Citation
Maddox D,
Collin GB,
Ikeda A,
Pratt CH,
Ikeda S,
Johnson B,
Hurd RE,
Shopland L,
Naggert JK,
Chang B,
Krebs MP,
Nishina PM.
A Mutation in Syne2 Causes Early Retinal Defects in Photoreceptors, Secondary Neurons, and Müller Glia. Invest Ophthalmol Vis Sci 2015 Jun; 56(6):3776-87.