Abstract

Cyclic nucleotide-gated (CNG) channels are important mediators in the transduction pathways of rod and cone photoreceptors and olfactory receptor neurons. Native CNG channels are composed of homologous A and B subunits. In heterologous expression systems, B subunits alone cannot form functional CNG channels, but they confer a number of channel properties when coexpressed with A subunits. To investigate the importance of the CNGB subunits in vivo, we deleted the CNGB1 gene in mice by gene targeting and homologous recombination. In the absence of CNGB1 in the rods, only trace amounts of the CNGA1 subunit were found in the rod outer segment. In electroretinograms (ERGs) CNGB1 KO-mice showed no rod-mediated responses. The rods also showed a slow-progressing degeneration caused by apoptotic death and concurred by retinal gliosis. Cones were primarily unaffected, but they started to degenerate after 6 months. At the age of about one year, CNGB1 KO-animals were lacking both rods and cones. Our results show that CNGB1 is a crucial determinant of native CNG channel targeting. As a result of the lack of rod CNG channels, CNGB1 KO-mice develop a retinal degeneration that resembles human retinitis pigmentosa.