Generation, identification and functional characterization of the nob4 mutation of Grm6 in the mouse

Lawrence H. Pinto, Martha H. Vitaterna, Kazuhiro Shimomura, Sandra M. Siepka, Victoria Balannik, Erin L. McDearmon, Chiaki Omura, Stephen Lumayag, Brandon M. Invergo, Brett Glawe, Donald R. Cantrell, Samsoon Inayat, Marissa A. Olvera, Kirstan A. Vessey, Maureen A. McCall, Dennis Maddox, Catherine W. Morgans, Brandon Young, Mathew T. Pletcher, Robert F. Mullins & 2 others John B. Troy, Joseph S. Takahashi

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)111-123
Number of pages13
JournalVisual Neuroscience
Volume24
Issue number1
DOIs
StatePublished - Jan 2007

Fingerprint

Mutation
Ethylnitrosourea
Chromosomes, Human, Pair 11
Contrast Sensitivity
Metabotropic Glutamate Receptors
Retinal Ganglion Cells
Inbred C57BL Mouse
Mutagenesis
Ganglia
Genes
Visual Acuity
Oocytes
Glutamic Acid
Proteins
Nucleotides
Genome
Ligands
Phenotype
Messenger RNA
metabotropic glutamate receptor 6

Keywords

  • Chemical mutagenesis
  • Congenital stationary night blindness
  • Depolarizing bipolar cells
  • Forward genetics
  • Gene discovery
  • Molecular cloning
  • ON pathway
  • Positional cloning
  • Retina
  • Retinal ganglion cells
  • Rod pathway
  • Visual acuity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Generation, identification and functional characterization of the nob4 mutation of Grm6 in the mouse. / Pinto, Lawrence H.; Vitaterna, Martha H.; Shimomura, Kazuhiro; Siepka, Sandra M.; Balannik, Victoria; McDearmon, Erin L.; Omura, Chiaki; Lumayag, Stephen; Invergo, Brandon M.; Glawe, Brett; Cantrell, Donald R.; Inayat, Samsoon; Olvera, Marissa A.; Vessey, Kirstan A.; McCall, Maureen A.; Maddox, Dennis; Morgans, Catherine W.; Young, Brandon; Pletcher, Mathew T.; Mullins, Robert F.; Troy, John B.; Takahashi, Joseph S.

In: Visual Neuroscience, Vol. 24, No. 1, 01.2007, p. 111-123.

Research output: Contribution to journalArticle

Pinto, LH, Vitaterna, MH, Shimomura, K, Siepka, SM, Balannik, V, McDearmon, EL, Omura, C, Lumayag, S, Invergo, BM, Glawe, B, Cantrell, DR, Inayat, S, Olvera, MA, Vessey, KA, McCall, MA, Maddox, D, Morgans, CW, Young, B, Pletcher, MT, Mullins, RF, Troy, JB & Takahashi, JS 2007, 'Generation, identification and functional characterization of the nob4 mutation of Grm6 in the mouse', Visual Neuroscience, vol. 24, no. 1, pp. 111-123. https://doi.org/10.1017/S0952523807070149
Pinto LH, Vitaterna MH, Shimomura K, Siepka SM, Balannik V, McDearmon EL et al. Generation, identification and functional characterization of the nob4 mutation of Grm6 in the mouse. Visual Neuroscience. 2007 Jan;24(1):111-123. https://doi.org/10.1017/S0952523807070149
Pinto, Lawrence H. ; Vitaterna, Martha H. ; Shimomura, Kazuhiro ; Siepka, Sandra M. ; Balannik, Victoria ; McDearmon, Erin L. ; Omura, Chiaki ; Lumayag, Stephen ; Invergo, Brandon M. ; Glawe, Brett ; Cantrell, Donald R. ; Inayat, Samsoon ; Olvera, Marissa A. ; Vessey, Kirstan A. ; McCall, Maureen A. ; Maddox, Dennis ; Morgans, Catherine W. ; Young, Brandon ; Pletcher, Mathew T. ; Mullins, Robert F. ; Troy, John B. ; Takahashi, Joseph S. / Generation, identification and functional characterization of the nob4 mutation of Grm6 in the mouse. In: Visual Neuroscience. 2007 ; Vol. 24, No. 1. pp. 111-123.
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AU - Shimomura, Kazuhiro

AU - Siepka, Sandra M.

AU - Balannik, Victoria

AU - McDearmon, Erin L.

AU - Omura, Chiaki

AU - Lumayag, Stephen

AU - Invergo, Brandon M.

AU - Glawe, Brett

AU - Cantrell, Donald R.

AU - Inayat, Samsoon

AU - Olvera, Marissa A.

AU - Vessey, Kirstan A.

AU - McCall, Maureen A.

AU - Maddox, Dennis

AU - Morgans, Catherine W.

AU - Young, Brandon

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AU - Mullins, Robert F.

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