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Identification of a new mutant allele, Grm6nob7, for complete congenital stationary night blindness

Published online by Cambridge University Press:  11 May 2015

HAOHUA QIAN ,
RUI JI ,
RONALD G. GREGG  and
NEAL S. PEACHEY
HAOHUA QIAN
Affiliation:
Visual Function Core, National Eye Institute, National Institutes of Health, Bethesda, Maryland
RUI JI
Affiliation:
Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, Kentucky
RONALD G. GREGG
Affiliation:
Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, Kentucky Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky
NEAL S. PEACHEY*
Affiliation:
Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio
*
*Address correspondence to: Neal Peachey, Cole Eye Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195. E-mail: peachen@ccf.org
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Abstract

Electroretinogram (ERG) studies identified a new mouse line with a normal a-wave but lacking the b-wave component. The ERG phenotype of this new allele, nob7, matched closely that of mouse mutants for Grm6, Lrit3, Trpm1, and Nyx, which encode for proteins expressed in depolarizing bipolar cells (DBCs). To identify the underlying mutation, we first crossed nob7 mice with Grm6nob3 mutants and measured the ERGs in offspring. All the offspring lacked the b-wave, indicating that nob7 is a new allele for Grm6: Grm6nob7. Sequence analyses of Grm6nob7 cDNAs identified a 28 base pair insertion between exons 8 and 9, which would result in a frameshift mutation in the open reading frame that encodes the metabotropic glutamate receptor 6 (Grm6). Sequencing both the cDNA and genomic DNA from exon 8 and intron 8, respectively, from the Grm6nob7 mouse revealed a G to A transition at the last position in exon 8. This mutation disrupts splicing and the normal exon 8 is extended by 28 base pairs, because splicing occurs 28 base pairs downstream at a cryptic splice donor. Consistent with the impact of the resulting frameshift mutation, there is a loss of mGluR6 protein (encoded by Grm6) from the dendritic tips of DBCs in the Grm6nob7 retina. These results indicate that Grm6nob7 is a new model of the complete form of congenital stationary night blindness, a human condition that has been linked to mutations of GRM6.

Keywords

Congenital stationary night blindnessElectroretinogramMetabotropic glutamate receptor 6
Type
Research Article
Information
Visual Neuroscience , Volume 32 , 2015 , E004
Copyright
Copyright © Cambridge University Press 2015 

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