Untersuchungen zur physiologischen Rolle von B-Untereinheiten zyklonukleotid-aktivierter Kationenkanäle anhand einer CNGB1-defizienten Mauslinie

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.