Abstract
Purpose: :
Mutations in the Cacna1f gene, which encodes the pore-forming α1 subunit of a voltage-gated calcium channel, are known to cause the incomplete form of X-linked congenital stationary night blindness (CSNB2). Recently, a novel mutation in Cacna1f was found in a New Zealand family, whose members showed unique CSNB2-like clinical features. The aim of this study was to investigate the effects of the identified mutation.
Methods: :
Two transgenic mouse lines were generated, one featuring the I745T mutation (Frodo), and a related line (Sam) producing a truncated presumably non-functional protein. The retinae of the mice were analysed immunocytochemically and their functional integrity was examined using the Ganzfeld electroretinogram (ERG). Scotopic and photopic flash ERGs were obtained. In addition, photopic flicker ERG responses were recorded.
Results: :
In the Frodo line, labelling of the α1 subunit was only present in very young mice and decreased rapidly with age. In addition, a loss of photoreceptors was observed in ageing Frodo mice. The truncated protein expressed in Sam mice was visible in protein staining. Heterozygous females of both strains showed mosaics in the labelling of the α1 subunit protein, indicating that the Cacna1f allele is subject to X-inactivation. The ERGs revealed strongly altered scotopic responses in both homo- and hemizygous individuals of both strains. In addition, photopic flash and flicker ERGs were hardly recordable. Surprisingly, Frodo mice displayed more strongly affected ERGs than Sam mice despite the more subtle mutation. The heterozygous females of both strains displayed larger ERG responses that were, however, smaller than those found in wild type mice.
Conclusions: :
The physiological and immunocytochemical findings suggest that in both transgenic mouse lines rod and cone pathways are affected. The ERG changes indicate substantial deficits already at the synaptic transmission from photoreceptors to second-order neurons.
Keywords: photoreceptors • electroretinography: non-clinical • synapse