New mouse models for recessive retinitis pigmentosa caused by mutations in the Pde6a gene.
Document Type
Article
Publication Date
2009
Keywords
Animals, Base-Sequence, Cyclic-GMP, Cyclic-Nucleotide-Phosphodiesterases-Type-6, Disease-Models-Animal, Eye-Proteins, Genes-Recessive, Mice-Inbred-A, Mice-Inbred-C57BL, Mice-Inbred-DBA, Molecular-Sequence-Data, Mutagenesis, Photoreceptor-Cells-Vertebrate, Retinitis-Pigmentosa
First Page
178
Last Page
192
JAX Source
Hum Mol Genet 2009 Jan; 18(1):178-92.
Abstract
The heterotetrameric phosphodiesterase (PDE) 6 complex, made up of alpha, beta and two gamma subunits, regulates intracellular cGMP levels by hydrolyzing cGMP in response to light activation of G protein coupled receptors in cones and rods, making it an essential component of the visual phototransduction cascade [Zhang, X. and Cote, R.H. (2005) cGMP signaling in vertebrate retinal photoreceptor cells. Front. Biosci., 10, 1191-1204.]. Using a genetic positional candidate cloning strategy, we have identified missense mutations within the catalytic domain of the Pde6a gene in two mouse models from an ethyl nitrosourea chemical mutagenesis screen. In these first small rodent models of PDE6A, significantly different biochemical outcomes and rates of degeneration of murine photoreceptor cells were observed, indicating allelic variation and previously unrecognized structure-function relationships. In addition, these new models reveal that the mutations not only affect the function of the PDE6A protein itself, but also the level of PDE6B within the retina. Finally, we show that the variation of the disease phenotype by background modifier genes may be dependent upon the particular disease allele present.
Recommended Citation
Sakamoto K,
McCluskey M,
Wensel TG,
Naggert JK,
Nishina PM.
New mouse models for recessive retinitis pigmentosa caused by mutations in the Pde6a gene. Hum Mol Genet 2009 Jan; 18(1):178-92.