title: Generation, identification and functional characterization of the nob4 mutation of Grm6 in the mouse.
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.
authors: Department of Neurobiology and Physiology and Center for Functional Genomics, Northwestern University, Evanston, Illinois 60208, USA. larry-pinto@northwestern.edu
authors: Lawrence H
authors: LH
authors: Pinto
authors: Martha H
authors: MH
authors: Vitaterna
authors: Kazuhiro
authors: K
authors: Shimomura
authors: Sandra M
authors: SM
authors: Siepka
authors: Victoria
authors: V
authors: Balannik
authors: Erin L
authors: EL
authors: McDearmon
authors: Chiaki
authors: C
authors: Omura
authors: Stephen
authors: S
authors: Lumayag
authors: Brandon M
authors: BM
authors: Invergo
authors: Brett
authors: B
authors: Glawe
authors: Donald R
authors: DR
authors: Cantrell
authors: Samsoon
authors: S
authors: Inayat
authors: Marissa A
authors: MA
authors: Olvera
authors: Kirstan A
authors: KA
authors: Vessey
authors: Maureen A
authors: MA
authors: McCall
authors: Dennis
authors: D
authors: Maddox
authors: Catherine W
authors: CW
authors: Morgans
authors: Brandon
authors: B
authors: Young
authors: Mathew T
authors: MT
authors: Pletcher
authors: Robert F
authors: RF
authors: Mullins
authors: John B
authors: JB
authors: Troy
authors: Joseph S
authors: JS
authors: Takahashi
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D003624:Darkness; D004596:Electroretinography / Q000379:methods; D005038:Ethylnitrosourea / Q000494:pharmacology; D005451:Fluorescein Angiography; D005838:Genotype; D051379:Mice; D008810:Mice, Inbred C57BL; D016297:Mutagenesis, Site-Directed; D009153:Mutagens; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*; D012160:Retina / Q000502:physiology
chemical_list: D009153:Mutagens; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; C113897:metabotropic glutamate receptor 6; D005038:Ethylnitrosourea