title: Impaired channel targeting and retinal degeneration in mice lacking the cyclic nucleotide-gated channel subunit CNGB1.
abstract: 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 approximately 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.
authors.affiliation: Department Pharmazie, Pharmakologie für Naturwissenschaften, Ludwig-Maximilians-Universität München, D-81377 München, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hüttl
authors.forename: Stylianos
authors.initials: S
authors.lastname: Michalakis
authors.forename: Mathias
authors.initials: M
authors.lastname: Seeliger
authors.forename: Dong-Gen
authors.initials: DG
authors.lastname: Luo
authors.forename: Niyazi
authors.initials: N
authors.lastname: Acar
authors.forename: Heidi
authors.initials: H
authors.lastname: Geiger
authors.forename: Kristiane
authors.initials: K
authors.lastname: Hudl
authors.forename: Robert
authors.initials: R
authors.lastname: Mader
authors.forename: Silke
authors.initials: S
authors.lastname: Haverkamp
authors.forename: Markus
authors.initials: M
authors.lastname: Moser
authors.forename: Alexander
authors.initials: A
authors.lastname: Pfeifer
authors.forename: Andrea
authors.initials: A
authors.lastname: Gerstner
authors.forename: King-Wai
authors.initials: KW
authors.lastname: Yau
authors.forename: Martin
authors.initials: M
authors.lastname: Biel
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D054815:Cyclic Nucleotide-Gated Cation Channels; D004596:Electroretinography; D005091:Exons; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D007473:Ion Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009457:Neuroglia / Q000473:pathology; D012160:Retina / Q000473:pathology / Q000502:physiology*; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology; D012374:Rod Cell Outer Segment / Q000378:metabolism; D014785:Vision, Ocular / Q000502:physiology
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D005136:Eye Proteins; D007473:Ion Channels