Myosin 6 is required for iris development and normal function of the outer retina.
Document Type
Article
Publication Date
11-1-2013
JAX Source
Invest Ophthalmol Vis Sci. 2013 Nov 1; 54(12):7223-33.
Volume
54
Issue
12
First Page
7223
Last Page
7233
ISSN
1552-5783
PMID
24106123
Abstract
PURPOSE: To determine the molecular basis and the pathologic consequences of a chemically induced mutation in the translational vision research models 89 (tvrm89) mouse model with ERG defects.
METHODS: Mice from a G3 N-ethyl-N-nitrosourea mutagenesis program were screened for behavioral abnormalities and defects in retinal function by ERGs. The chromosomal position for the recessive tvrm89 mutation was determined in a genome-wide linkage analysis. The critical region was refined, and candidate genes were screened by direct sequencing. The tvrm89 phenotype was characterized by circling behavior, in vivo ocular imaging, detailed ERG-based studies of the retina and RPE, and histological analysis of these structures.
RESULTS: The tvrm89 mutation was localized to a region on chromosome 9 containing Myo6. Sequencing identified a T→C point mutation in the codon for amino acid 480 in Myo6 that converts a leucine to a proline. This mutation does not confer a loss of protein expression levels; however, mice homozygous for the Myo6(tvrm89) mutation display an abnormal iris shape and attenuation of both strobe-flash ERGs and direct-current ERGs by 4 age weeks, neither of which is associated with photoreceptor loss.
CONCLUSIONS: The tvrm89 phenotype mimics that reported for Myosin6-null mice, suggesting that the mutation confers a loss of myosin 6 protein function. The observation that homozygous Myo6(tvrm89) mice display reduced ERG a-wave and b-wave components, as well as components of the ERG attributed to RPE function, indicates that myosin 6 is necessary for the generation of proper responses of the outer retina to light.
Invest Ophthalmol Vis Sci. 2013 Nov 1; 54(12):7223-33.
Recommended Citation
Samuels I,
Bell B,
Sturgill-Short G,
Ebke L,
Rayborn M,
Shi L,
Nishina PM,
Peachey N.
Myosin 6 is required for iris development and normal function of the outer retina. Invest Ophthalmol Vis Sci. 2013 Nov 1; 54(12):7223-33.