title: A novel middle-wavelength opsin (M-opsin) null-mutation in the retinal cone dysfunction rat.
abstract: The disease-causing gene which underlies a naturally occurring X-linked mutant cone dysfunction Sprague-Dawley rat model was investigated. Full-field electroretinogram (ERG) and simple sequence length polymorphism analyses were applied to 441-second filial generation rats that were derived from crossing a mutant rat and a Brown-Norway rat. After identifying a mutation mapping within the telomeric region of chromosome X, a candidate gene related to retinal cone function in this region was further screened using real-time PCR, immunohistochemistry and histological methods. The results showed that a G-to-T substitution at the splice acceptor site of intron 4 was present in the opsin 1, medium-wave sensitive (Opn1mw) gene, thereby causing down-regulated transcription and translation. These changes were consistent with abnormities seen in the ERG response. However, there was no significant histological change in the mutant rat retina. Therefore, we infer from this that the causative gene for the mutation is Opn1mw and consequently term this a middle-wavelength opsin cone dysfunction (MCD) rat model. The deficiency in vision of the MCD rat is similar to the color vision defects that occur in humans with a color vision defect but without recessive retinal degeneration. This rat model may be useful for understanding the mechanism that is responsible for color vision and for developing clinical therapies for several retinal dystrophies caused by cone opsin deficiencies.
authors.affiliation: Department of Clinical Aerospace Medicine, Faculty of Aerospace Medicine, Key Laboratory of Aerospace Medicine of National Education Ministry, Fourth Military Medical University, 17 Changle West Road, Xi'an 710032, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Xie
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakanishi
authors.forename: Qun
authors.initials: Q
authors.lastname: Guo
authors.forename: Feng
authors.initials: F
authors.lastname: Xia
authors.forename: Guolin
authors.initials: G
authors.lastname: Yan
authors.forename: Jing
authors.initials: J
authors.lastname: An
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Tadao
authors.initials: T
authors.lastname: Serikawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuramoto
authors.forename: Zuoming
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003117:Color Vision Defects / Q000235:genetics* / Q000503:physiopathology; D003623:Dark Adaptation; D004195:Disease Models, Animal; D015536:Down-Regulation; D004596:Electroretinography; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D019084:Fluorescent Antibody Technique, Indirect; D008297:Male; D017354:Point Mutation / Q000235:genetics*; D051381:Rats; D011914:Rats, Inbred BN; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000503:physiopathology*; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D012162:Retinal Degeneration / Q000235:genetics* / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017299:Rod Opsins / Q000235:genetics*
chemical_list: D017299:Rod Opsins; C095854:middle-wavelength opsin; D016650:Fluorescein-5-isothiocyanate