1. Impaired Channel Targeting and Retinal Degeneration in Mice Lacking the Cyclic Nucleotide-Gated Channel Subunit CNGB1
- Author
-
Silke Haverkamp, Martin Biel, Stylianos Michalakis, Mathias W. Seeliger, Andrea Gerstner, Niyazi Acar, King Wai Yau, Heidi Geiger, Robert Mader, Sabine Hüttl, Dong Gen Luo, Kristiane Hudl, Alexander Pfeifer, Markus Moser, Ludwig Maximilians University of Munich, University Eye Hospital Tuebingen, Johns Hopkins University (JHU), Centre des Sciences du Goût et de l'Alimentation (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Department of Neuroanatomy, Universität Leipzig [Leipzig], Max Planck Institute of Biochemistry (MPIB), and Max-Planck-Gesellschaft
- Subjects
Retinal degeneration ,genetic structures ,Apoptosis ,CONES (RETINA)PATHOLOGY ,EYE ,P.H.S ,Ion Channels ,RETINAL DEGENERATION GENETICS ,GENE DELETION ,RESEARCH SUPPORT ,chemistry.chemical_compound ,0302 clinical medicine ,Retinal Rod Photoreceptor Cells ,[SDV.IDA]Life Sciences [q-bio]/Food engineering ,CHANNELS BIOSYNTHESIS GENETICS PHYSIOLOGY ,Cyclic nucleotide-gated ion channel ,Mice, Knockout ,Genetics ,0303 health sciences ,medicine.diagnostic_test ,General Neuroscience ,Retinal Degeneration ,ROD OUTER ,Rod Cell Outer Segment ,Cell biology ,APOPTOSIS GENETICS ,NEUROLOGIA PATHOLOGY ,Retinal Cone Photoreceptor Cells ,EXONS ,Neuroglia ,Protein subunit ,PHOTOTRANSDUCTION PHYSILOGY ,Cyclic Nucleotide-Gated Cation Channels ,Biology ,PROTEINS BIOSYNTHESIS GENETICS ,SEGMENTS METABOLISM ,Article ,Retina ,N.I.H ,EXTRAMURAL ,03 medical and health sciences ,RODS(RETINA)PATHOLOGY ,Retinitis pigmentosa ,medicine ,[SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering ,ION ,Eye Proteins ,PHYSIOLOGY ,Vision, Ocular ,030304 developmental biology ,ANIMALS ,Retinal ,GENETIQUE ,INBRED C57BL ,medicine.disease ,Mice, Inbred C57BL ,MICE ,KNOCKOUT ,RETINA PATHOLOGY AND PHYSIOLOGY ,chemistry ,ELECTRORETINOGRAPHY ,sense organs ,030217 neurology & neurosurgery ,Electroretinography - 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 subunitsin vivo, we deleted theCNGB1gene 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 lackingCNGB1(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.
- Published
- 2005
- Full Text
- View/download PDF