Selective Loss Of ERG b–Wave Caused By An Autosomal Recessive Mutation In Mice.

Abstract

Abstract: : Purpose:A selective loss of ERG b–wave was discovered in a mouse strain with a transgene TgN(Igh2^k3–83). Here we report the clinical appearance, histology, chromosomal localization, and mutant gene identification of a new hereditary model of no b–wave (nob3). Methods:We characterized the clinical effects of this mutation using serial indirect ophthalmoscopy, fundus photography, electroretinography (ERG), and histology, and performed genetic analysis including linkage studies and gene identification. Results:Mice homozygous for the nob3 mutation show a normal fundus and histology, but no rod ERG b–wave and a poor cone ERG can be detected by 3 weeks of age. Genetic analysis showed that the phenotype is not caused by the transgene TgN(Igh2^k3–83). nob3 is an autosomal recessive mutation that maps to mouse Chromosome 11 closely linked to D11Mit139 at position 23 cM where the mouse gamma–aminobutyric acid (GABA–A) receptor, subunit alpha 6 (Gabra6) gene is located. Sequence analysis shows that the loss of the rod ERG b–wave is caused by a missense mutation in exon 3 of the Gabra6 gene and the gene symbol for the nob3 mutation has been changed to Gabra6^nob3. Conclusions:A missense mutation in the mouse gamma–aminobutyric acid (GABA–A) receptor, subunit alpha 6 (Gabra6) gene causing loss of the rod ERG b–wave is a novel finding. The phenotype of the mice with the nob3 mutation is similar to the mice with the nob mutation that is a mouse model of CSNB1. The nob3/nob3 mutant provides a mouse model to study mechanism associated with this type of disease in human.

Keywords: electroretinography: non–clinical • gene mapping • candidate gene analysis