title: GARP2 accelerates retinal degeneration in rod cGMP-gated cation channel β-subunit knockout mice.
abstract: The Cngb1 locus-encoded β-subunit of rod cGMP-gated cation channel and associated glutamic acid rich proteins (GARPs) are required for phototransduction, disk morphogenesis, and rod structural integrity. To probe individual protein structure/function of the GARPs, we have characterized several transgenic mouse lines selectively restoring GARPs on a Cngb1 knockout (X1-/-) mouse background. Optical coherence tomography (OCT), light and transmission electron microscopy (TEM), and electroretinography (ERG) were used to analyze 6 genotypes including WT at three and ten weeks postnatal. Comparison of aligned histology/OCT images demonstrated that GARP2 accelerates the rate of degeneration. ERG results are consistent with the structural analyses showing the greatest attenuation of function when GARP2 is present. Even 100-fold or more overexpression of GARP1 could not accelerate degeneration as rapidly as GARP2, and when co-expressed GARP1 attenuated the structural and functional deficits elicited by GARP2. These results indicate that the GARPs are not fully interchangeable and thus, likely have separate and distinct functions in the photoreceptor. We also present a uniform murine OCT layer naming nomenclature system that is consistent with human retina layer designations to standardize murine OCT, which will facilitate data evaluation across different laboratories.
authors.affiliation: Departments of Optometry and Vision Science, University of Alabama at Birmingham, 1670 University Blvd, VH 375, Birmingham, AL 35294-0019, USA.
authors.forename: Marci L
authors.initials: ML
authors.lastname: DeRamus
authors.affiliation: Departments of Optometry and Vision Science, University of Alabama at Birmingham, 1670 University Blvd, VH 375, Birmingham, AL 35294-0019, USA.
authors.forename: Delores A
authors.initials: DA
authors.lastname: Stacks
authors.affiliation: Departments of Optometry and Vision Science, University of Alabama at Birmingham, 1670 University Blvd, VH 375, Birmingham, AL 35294-0019, USA.
authors.forename: Youwen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, University of Alabama at Birmingham, 700 18th Street South, Suite 609, Birmingham, AL 35294, USA.
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Huisingh
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Ryals Public Health Building, 1665 University Boulevard, Birmingham, AL 35294, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: McGwin
authors.affiliation: Departments of Optometry and Vision Science, University of Alabama at Birmingham, 1670 University Blvd, VH 375, Birmingham, AL 35294-0019, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Pittler
mesh_terms: D000483:Alleles; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004596:Electroretinography; D023061:Gene Order; D056426:Genetic Loci; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout; D008853:Microscopy; D009419:Nerve Tissue Proteins / Q000172:deficiency*; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D041623:Tomography, Optical Coherence
chemical_list: C529481:Cngb1 protein, mouse; D054815:Cyclic Nucleotide-Gated Cation Channels; D009419:Nerve Tissue Proteins; D006152:Cyclic GMP