A naturally-occurring mutation in Cacna1f in a rat model of congenital stationary night blindness

Purpose: To identify the gene mutation responsible for a previously described rat model of X-linked congenital stationary night blindness (CSNB). Methods: Rat orthologous genes for Nyx and Cacnalf were isolated from retina through rapid amplification the cDNA ends (RACE) and examined for mutations. Electroretinograms were used to identify affected animals. Results: The rat Nyx cDNA spans 1,971 nucleotides and encodes a protein of 476 amino acid (GenBank: DQ393414). The rat Cacnalf cDNA spans 6,076 nucleotides and encodes a protein of 1,980 amino acids (GenBank: DQ393415). A c.2941C>T (p.R981Stop) mutation in Cacnalf was found in affected rats. Immunochemistry study showed labeling for rod bipolar and horizontal cells were reduced in affect retinas. For affected rats, b-wave and oscillatory potentials of scotopic ERG were absent, and b-wave of photopic ERG was clear but obviously reduced. Conclusions: The Cacnalf mutation identified in the rat model of CSNB was predicted to lead to a protein product that is shortened by 999 amino acids, indicating that this is a model for the incomplete subtype of human X-linked CSNB (CSNB2). This rat model will be useful for defining the pathophysiological properties of this human disorder.