Journal article
Generation, identification and functional characterization of the nob4 mutation of Grm6 in the mouse
Visual neuroscience, Vol.24(1), pp.111-123
01/2007
DOI: 10.1017/S0952523807070149
PMCID: PMC3770726
PMID: 17430614
Abstract
We performed genome-wide chemical mutagenesis of C57BL/6J mice using N-ethyl-N-nitrosourea (ENU). Electroretinographic screening of the third generation offspring revealed two G3 individuals from one G1 family with a normal a-wave but lacking the b-wave that we named nob4. The mutation was transmitted with a recessive mode of inheritance and mapped to chromosome 11 in a region containing the Grm6 gene, which encodes a metabotropic glutamate receptor protein, mGluR6. Sequencing confirmed a single nucleotide substitution from T to C in the Grm6 gene. The mutation is predicted to result in substitution of Pro for Ser at position 185 within the extracellular, ligand-binding domain and oocytes expressing the homologous mutation in mGluR6 did not display robust glutamate-induced currents. Retinal mRNA levels for Grm6 were not significantly reduced, but no immunoreactivity for mGluR6 protein was found. Histological and fundus evaluations of nob4 showed normal retinal morphology. In contrast, the mutation has severe consequences for visual function. In nob4 mice, fewer retinal ganglion cells (RGCs) responded to the onset (ON) of a bright full field stimulus. When ON responses could be evoked, their onset was significantly delayed. Visual acuity and contrast sensitivity, measured with optomotor responses, were reduced under both photopic and scotopic conditions. This mutant will be useful because its phenotype is similar to that of human patients with congenital stationary night blindness and will provide a tool for understanding retinal circuitry and the role of ganglion cell encoding of visual information.
Details
- Title: Subtitle
- Generation, identification and functional characterization of the nob4 mutation of Grm6 in the mouse
- Creators
- Lawrence H Pinto - Department of Neurobiology and Physiology and Center for Functional Genomics, Northwestern University, Evanston, Illinois 60208, USA. larry-pinto@northwestern.eduMartha H VitaternaKazuhiro ShimomuraSandra M SiepkaVictoria BalannikErin L McDearmonChiaki OmuraStephen LumayagBrandon M InvergoBrett GlaweDonald R CantrellSamsoon InayatMarissa A OlveraKirstan A VesseyMaureen A McCallDennis MaddoxCatherine W MorgansBrandon Young - Scripps Research InstituteMathew T PletcherRobert F MullinsJohn B TroyJoseph S Takahashi
- Resource Type
- Journal article
- Publication Details
- Visual neuroscience, Vol.24(1), pp.111-123
- DOI
- 10.1017/S0952523807070149
- PMID
- 17430614
- PMCID
- PMC3770726
- NLM abbreviation
- Vis Neurosci
- ISSN
- 0952-5238
- eISSN
- 1469-8714
- Publisher
- England
- Grant note
- U01 MH061915-03 / NIMH NIH HHS Howard Hughes Medical Institute U01MH61915 / NIMH NIH HHS U01 MH061915-04 / NIMH NIH HHS R01 EY014701 / NEI NIH HHS U01 MH061915-01A1 / NIMH NIH HHS R01 EY06669 / NEI NIH HHS U01 MH061915-05 / NIMH NIH HHS R01 EY006669 / NEI NIH HHS U01 MH061915-02 / NIMH NIH HHS U01 MH061915 / NIMH NIH HHS R01 EY012354 / NEI NIH HHS
- Language
- English
- Date published
- 01/2007
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9983980049602771
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