TY - JOUR
T1 - Impaired channel targeting and retinal degeneration in mice lacking the cyclic nucleotide-gated channel subunit CNGB1
AU - Hüttl, Sabine
AU - Michalakis, Stylianos
AU - Seeliger, Mathias
AU - Luo, Dong Gen
AU - Acar, Niyazi
AU - Geiger, Heidi
AU - Hudl, Kristiane
AU - Mader, Robert
AU - Haverkamp, Silke
AU - Moser, Markus
AU - Pfeifer, Alexander
AU - Gerstner, Andrea
AU - Yau, King Wai
AU - Biel, Martin
PY - 2005/1/5
Y1 - 2005/1/5
N2 - Cyclic nucleotide-gated (CNG) channels are important mediators in the transduction pathways of rod and cone photoreceptors. Native CNG channels are heterotetramers 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. In the absence of CNGB1, only trace amounts of the CNGA1 subunit were found on the rod outer segment. As a consequence, the vast majority of isolated rod photoreceptors in mice lacking CNGB1 (CNGB1-/-) failed to respond to light. In electroretinograms (ERGs), CNGB1-/- 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 and showed normal ERG responses up to 6 months, but they started to degenerate in later stages. At the age of ∼1 year, CNGB1-/- animals were devoid of 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-/- mice develop a retinal degeneration that resembles human retinitis pigmentosa.
AB - Cyclic nucleotide-gated (CNG) channels are important mediators in the transduction pathways of rod and cone photoreceptors. Native CNG channels are heterotetramers 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. In the absence of CNGB1, only trace amounts of the CNGA1 subunit were found on the rod outer segment. As a consequence, the vast majority of isolated rod photoreceptors in mice lacking CNGB1 (CNGB1-/-) failed to respond to light. In electroretinograms (ERGs), CNGB1-/- 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 and showed normal ERG responses up to 6 months, but they started to degenerate in later stages. At the age of ∼1 year, CNGB1-/- animals were devoid of 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-/- mice develop a retinal degeneration that resembles human retinitis pigmentosa.
KW - Apoptosis
KW - CNGB1
KW - Channel trafficking
KW - Cyclic nucleotide-gated channel
KW - Retinitis pigmentosa
KW - Rod photoreceptor
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U2 - 10.1523/JNEUROSCI.3764-04.2005
DO - 10.1523/JNEUROSCI.3764-04.2005
M3 - Article
C2 - 15634774
AN - SCOPUS:19944428767
SN - 0270-6474
VL - 25
SP - 130
EP - 138
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 1
ER -