This mutant provides a model for retinitis pigmentosa 20 and Leber congenital amaurosis 2, is useful in the study of the visual cycle, and has been used successfully in gene therapy experiments.Read More +
This mutant provides a model for retinitis pigmentosa 20 and Leber congenital amaurosis. There is slow retinal degeneration as assessed by histology, but rod ERG readings show profoundly diminished dark adapted responses by 1 month of age The light adapted ERG responses at 1 month are delayed and diminished amplitude occurs with age. At 3 months of age the fundus examination appears normal and at 5 months of age small, punctate, white spots appear beneath retinal vessels. At 15 months of age the fundus has a mildly pigmented granular and mottled appearance. Histology of the retina begins to show occasional voids in the outer segments of the photoreceptor cells at approximately 6 weeks of age and at 3 months of age the outer segments have more voids and are more disorganized but the outer segments and the outer nuclear layer remain predominantly intact and relatively normal. However, by 7 months the outer nuclear layer has 6 to 8 layers of outer nuclear layer remaining in the retina and the outer segments are noticeably shorter than normal, and at 27 months only 3 to 4 layers of the outer nuclear layer remain, the outer segments is significantly shorter than normal, and the retinal pigment epithelium is atrophied and hypopigmented. The retinal pigment epithelium shows small lipid-like droplets detectable by electron microscopy at 3 weeks of age and increasing in size and frequency at 3 months of age. Consistent with the disrupted function of RPE65 to convert all-trans retinal to 11-cis retinal, HPLC fails to detect 11-cis-retinal in the retinas of homozygotes, rhodopsin absorbance is not detectable from 2 weeks to 5 months of age, there is reduced opsin levels in retinas as early as 8 days of age, and a progressive increase in retinyl esters after 3 weeks of age.
The recessive rd12 mutation arose spontaneously in a male mouse of strain B6.A-H2-T18a/BoyEg (Stock No. 001166). This male was bred to a C57BL/6J female and their F1 female offspring were bred back to this male to identify homozygotes. rd12 was then further backcrossed onto C57BL/6J to generate this strain.
|Allele Name||retinal degeneration 12|
|Gene Symbol and Name||Rpe65, retinal pigment epithelium 65|
|Strain of Origin||B6.A-H2-T18a/BoyEgJ|
|Molecular Note||This spontaneous mutation was discovered during a routine strain screen at The Jackson Laboratory. Its mapping location suggested it might be an allele of Rpe65, and a point mutation was identified in the Rpe65 gene. The mutation is a base substitution C-to-T at coding nucleotide 130 resulting in a stop codon in stead of arginine at position 44 (p.R44*). Immunostaining revealed that mutant eyes do not express RPE65 protein, and subretinal injection of the AAV5-CBA viral vector expressing human RPE65 significantly rescued the visual phenotype for at least 7 months following treatment.|
When using the B6(A)-Rpe65rd12/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #005379 in your Materials and Methods section.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.