title: Morphological, physiological, and biochemical changes in rhodopsin knockout mice.
abstract: Mutations in rod opsin, the visual pigment protein of rod photoreceptors, account for approximately 15% of all inherited human retinal degenerations. However, the physiological and molecular events underlying the disease process are not well understood. One approach to this question has been to study transgenic mice expressing opsin genes containing defined mutations. A caveat of this approach is that even the overexpression of normal opsin leads to photoreceptor cell degeneration. To overcome the problem, we have reduced or eliminated endogenous rod opsin content by targeted gene disruption. Retinas in mice lacking both opsin alleles initially developed normally, except that rod outer segments failed to form. Within months of birth, photoreceptor cells degenerated completely. Retinas from mice with a single copy of the opsin gene developed normally, and rods elaborated outer segments of normal size but with half the normal complement of rhodopsin. Photoreceptor cells in these retinas also degenerated but did so over a much slower time course. Physiological and biochemical experiments showed that rods from mice with a single opsin gene were approximately 50% less sensitive to light, had accelerated flash-response kinetics, and contained approximately 50% more phosducin than wild-type controls.
authors.affiliation: New England Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA. jlem01@tuffs.edu
authors.forename: J
authors.initials: J
authors.lastname: Lem
authors.forename: N V
authors.initials: NV
authors.lastname: Krasnoperova
authors.forename: P D
authors.initials: PD
authors.lastname: Calvert
authors.forename: B
authors.initials: B
authors.lastname: Kosaras
authors.forename: D A
authors.initials: DA
authors.lastname: Cameron
authors.forename: M
authors.initials: M
authors.lastname: Nicolò
authors.forename: C L
authors.initials: CL
authors.lastname: Makino
authors.forename: R L
authors.initials: RL
authors.lastname: Sidman
mesh_terms: D000818:Animals; D004594:Electrophysiology; D005136:Eye Proteins / Q000235:genetics; D018390:Gene Targeting / Q000379:methods; D008027:Light; D051379:Mice; D018345:Mice, Knockout; D015591:Microspectrophotometry; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology; D012243:Rhodopsin / Q000235:genetics*; D017299:Rod Opsins / Q000235:genetics; D014785:Vision, Ocular / Q000235:genetics
chemical_list: D005136:Eye Proteins; D017299:Rod Opsins; D012243:Rhodopsin