title: Allelic variance between GRM6 mutants, Grm6nob3 and Grm6nob4 results in differences in retinal ganglion cell visual responses.
abstract: An electroretinogram (ERG) screen identified a mouse with a normal a-wave but lacking a b-wave, and as such it was designated no b-wave3 (nob3). The nob3 phenotype mapped to chromosome 11 in a region containing the metabotropic glutamate receptor 6 gene (Grm6). Sequence analyses of cDNA identified a splicing error in Grm6, introducing an insertion and an early stop codon into the mRNA of affected mice (designated Grm6(nob3)). Immunohistochemistry of the Grm6(nob3) retina showed that GRM6 was absent. The ERG and visual behaviour abnormalities of Grm6(nob3) mice are similar to Grm6(nob4) animals, and similar deficits were seen in compound heterozygotes (Grm6(nob4/nob3)), indicating that Grm6(nob3) is allelic to Grm6(nob4). Visual responses of Grm6(nob3) retinal ganglion cells (RGCs) to light onset were abnormal. Grm6(nob3) ON RGCs were rarely recorded, but when they were, had ill-defined receptive field (RF) centres and delayed onset latencies. When Grm6(nob3) OFF-centre RGC responses were evoked by full-field stimulation, significantly fewer converted that response to OFF/ON compared to Grm6(nob4) RGCs. Grm6(nob4/nob3) RGC responses verified the conclusion that the two mutants are allelic. We propose that Grm6(nob3) is a new model of human autosomal recessive congenital stationary night blindness. However, an allelic difference between Grm6(nob3) and Grm6(nob4) creates a disparity in inner retinal processing. Because the localization of GRM6 is limited to bipolar cells in the On pathway, the observed difference between RGCs in these mutants is likely to arise from differences in their inputs.
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Maddox
authors.forename: Kirstan A
authors.initials: KA
authors.lastname: Vessey
authors.forename: Gary L
authors.initials: GL
authors.lastname: Yarbrough
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Invergo
authors.forename: Donald R
authors.initials: DR
authors.lastname: Cantrell
authors.forename: Samsoon
authors.initials: S
authors.lastname: Inayat
authors.forename: Victoria
authors.initials: V
authors.lastname: Balannik
authors.forename: Wanda L
authors.initials: WL
authors.lastname: Hicks
authors.forename: Norman L
authors.initials: NL
authors.lastname: Hawes
authors.forename: Shannon
authors.initials: S
authors.lastname: Byers
authors.forename: Richard S
authors.initials: RS
authors.lastname: Smith
authors.forename: Ron
authors.initials: R
authors.lastname: Hurd
authors.forename: Douglas
authors.initials: D
authors.lastname: Howell
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Gregg
authors.forename: Bo
authors.initials: B
authors.lastname: Chang
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Naggert
authors.forename: John B
authors.initials: JB
authors.lastname: Troy
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Pinto
authors.forename: Patsy M
authors.initials: PM
authors.lastname: Nishina
authors.forename: Maureen A
authors.initials: MA
authors.lastname: McCall
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D004596:Electroretinography; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D010775:Photic Stimulation; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics* / Q000378:metabolism; D012160:Retina / Q000033:anatomy & histology / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000502:physiology*; D017422:Sequence Analysis, DNA; D014794:Visual Fields
chemical_list: D018094:Receptors, Metabotropic Glutamate; C113897:metabotropic glutamate receptor 6