| First Author | Fan J | Year | 2008 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 49 |
| Issue | 6 | Pages | 2384-9 |
| PubMed ID | 18296659 | Mgi Jnum | J:136882 |
| Mgi Id | MGI:3797303 | Doi | 10.1167/iovs.08-1727 |
| Citation | Fan J, et al. (2008) Rpe65-/- and Lrat-/- mice: comparable models of leber congenital amaurosis. Invest Ophthalmol Vis Sci 49(6):2384-9 |
| abstractText | PURPOSE: The Rpe65-/- mouse, used as a model for Leber congenital amaurosis, has slow rod degeneration and rapid cone loss, presumably because of the mistrafficking of cone opsins. This animal does not generate 11-cis retinal, and both cone loss and rod response are restored by 11-cis retinal administration. Similarly, the Lrat-/- mouse does not produce 11-cis retinal. The authors sought to determine whether the same effects on rod and cone opsins in the Rpe65-/- mouse are also present in the Lrat-/- mouse, thereby establishing that these changes can be attributed to the lack of 11-cis retinal rather than to some unknown function of RPE65. METHODS: Rod and cone opsins were localized by immunohistochemical methods. Functional opsin levels were determined by regeneration with 11-cis retinal. Isorhodopsin levels were determined from pigment extraction. Opsin phosphorylation was determined by mass spectrometry. RESULTS: Rods in both models degenerated slowly. Regenerable rod opsin levels were similar over the 6-month time course investigated, rod opsin was phosphorylated at a low level (approximately 10%), and minimal 9-cis retinal was generated by a nonphotic process, giving a trace light response. In both models, S-opsin and M/L-opsin failed to traffic to the cone outer segments appropriately, and rapid cone degeneration occurred. Cone opsin mistrafficking in both models was arrested on 11-cis retinal administration. CONCLUSIONS: These data show that the Lrat-/- and Rpe65-/- mice are comparable models for studies of Leber congenital amaurosis and that the destructive cone opsin mistrafficking is caused by the lack of 11-cis retinal. |
