B6.B10(D2)-Grm6^nob3/Boc

Stock number: 016883
Research areas: Sensorineural Research

Description

Visual responses of Grm6^nob3 retinal ganglion cells to light onset are abnormal, and immunohistochemistry of the Grm6^nob3 retina showed that GRM6 was absent. Grm6(nob3) may be useful as a new model of human autosomal recessive congenital stationary night blindness.

Detailed description

Although retinal sections are histologically normal, electroretinogram assessment of homozygotes shows near-normal a-wave but absent both scotopic and photopic b-waves. The contrast sensitivity and spatial frequency thresholds are reduced. Retinal ganglion cell ON responses have a longer latency than normal and fewer retinal ganglion cells respond to the bright phase of a full-field stimulus. There are fewer OFF-center retinal ganglion cells that have an ON response to a full-field stimulus, which is distinct from findings in mice homozygous for the no b-wave 4 (nob4) allele.

Development

Tg(Igh2^k3-83)1Nemz was generated in a mixed DBA/2J x C57BL/10J background, backcrossed to B10.D2/nSnJ for many generations and then backcrossed onto C57BL/10J. During the backcrossing to C57BL/10J the no b wave mutation was identified in an electroretinogram screen in the laboratory of Dr. Bo Chang at The Jackson Laboratory. This novel mutation was backcrossed onto C57BL/6J away from the transgene for 10 generations and then bred to homozygosity yielding this strain.

A C-to-T transition occured spontaneously in intron 1. This results in a new splice donor site (G-GT from G-GC), which alters splicing and, together with an upstream cryptic splice donor CAG, inserts a new 65 bp exon between exons 1 and 2. This leads to a frame shift and premature termination. The absence of protein expression was confirmed by immunohistochemistry on the outer plexiform layer.

Allele

Symbol: Grm6^nob3
Name: no b wave 3
MGI accession ID: MGI:3605835
Generation method: Spontaneous
Attributes: Null/Knockout
Marker symbol: Grm6
Marker name: glutamate receptor, metabotropic 6
Chromosome: 11
Strain of origin: C57BL/10
Molecular note: A C-to-T transition occured spontaneously in intron 1. This results in a new splice donor site (G-GT from G-GC), which alters splicing and, together with an upstream cryptic splice donor CAG, inserts a new 65 bp exon between exons 1 and 2. This leads to a frame shift and premature termination. The absence of protein expression was confirmed by immunohistochemistry on the outer plexiform layer.