Strain Name:

B6(A)-Rpe65rd12/J

Stock Number:

005379

Order this mouse

Availability:

Research Strain

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.

Description

Strain Information

Former Names B6(A)-rd12/J    (Changed: 14-JAN-05 )
Type Mutant Strain; Spontaneous Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse

Appearance
black, retinal degeneraton
Related Genotype: a/a Rpe65rd12/Rpe65rd12

Description
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.

Development
The recessive rd12 mutation arose spontaneously in a male mouse of strain B6.A-H2-T18a/BoyEg (stock #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.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Leber Congenital Amaurosis 2; LCA2
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Retinitis Pigmentosa 20; RP20   (RPE65)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Rpe65rd12/Rpe65rd12

        C57BL/6J
  • vision/eye phenotype
  • abnormal eye electrophysiology
    • electroretinographic (ERG) analysis reveals progressive loss of retinal function   (MGI Ref ID J:94549)
    • the ERG b-wave amplitude of mutant mice decreases as the mice age   (MGI Ref ID J:94549)
    • abnormal cone electrophysiology
      • the light-adapted ERG response is delayed and exhibits progressive diminution of amplitude with the age of the mice   (MGI Ref ID J:94549)
    • abnormal rod electrophysiology
      • by three weeks of age, homozygous mice exhibit a poor dark-adapted (rod) ERG response   (MGI Ref ID J:94549)
  • abnormal retinal rod cell outer segment morphology
    • light microscopic examination of eyes of 6 week-old mutant mice reveals occasional small voids in the rod outer segments, which become progressively larger and more numerous   (MGI Ref ID J:94549)
    • at 3 months of age, the rod outer segments are of normal thickness; by 27 months the rod outer segments are almost absent   (MGI Ref ID J:94549)
  • retinal degeneration
    • ophthalmoscopic examination of the fundus reveals small white spots evenly scattered across the mutant retina by 5 months of age; by 15 months, the fundus appears granular and mottled   (MGI Ref ID J:94549)
    • at 3 months of age, both the rod outer segments and the outer nuclear layer are of normal thickness; by 7 months, the outer nuclear layer is reduced by 30%, and by 27 months the rod outer segments are almost absent and the outer nuclear layer is only one-third normal thickness   (MGI Ref ID J:94549)
  • thin retinal outer nuclear layer
    • at 3 months of age, the outer nuclear layer is of normal thickness; by 7 months, the outer nuclear layer is reduced by 30%, and by 27 months the outer nuclear layer is only one-third normal thickness   (MGI Ref ID J:94549)
  • nervous system phenotype
  • abnormal retinal rod cell outer segment morphology
    • light microscopic examination of eyes of 6 week-old mutant mice reveals occasional small voids in the rod outer segments, which become progressively larger and more numerous   (MGI Ref ID J:94549)
    • at 3 months of age, the rod outer segments are of normal thickness; by 27 months the rod outer segments are almost absent   (MGI Ref ID J:94549)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Rpe65rd12 related

Research Tools
Sensorineural Research
      retinal degeneration

Sensorineural Research
Retinal Degeneration

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Rpe65rd12
Allele Name retinal degeneration 12
Allele Type Spontaneous
Strain of OriginB6.A-H2-T18a/BoyEgJ
Gene Symbol and Name Rpe65, retinal pigment epithelium 65
Chromosome 3
Gene Common Name(s) A930029L06Rik; LCA2; Mord1; RIKEN cDNA A930029L06 gene; RP20; mRPE65; modifier of retinal degeneration 1; rd12; retinal degeneration 12; sRPE65;
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 Cto T at position 130 resulting in a stop codon at amino acid 44. 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. [MGI Ref ID J:94549]

Genotyping

Genotyping Information


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Rpe65rd12 related

Berkowitz BA; Roberts R; Oleske DA; Chang M; Schafer S; Bissig D; Gradianu M. 2009. Quantitative mapping of ion channel regulation by visual cycle activity in rodent photoreceptors in vivo. Invest Ophthalmol Vis Sci 50(4):1880-5. [PubMed: 19060264]  [MGI Ref ID J:146669]

Budzynski E; Gross AK; McAlear SD; Peachey NS; Shukla M; He F; Edwards M; Won J; Hicks WL; Wensel TG; Naggert JK; Nishina PM. 2010. Mutations of the opsin gene (Y102H and I307N) lead to light-induced degeneration of photoreceptors and constitutive activation of phototransduction in mice. J Biol Chem 285(19):14521-33. [PubMed: 20207741]  [MGI Ref ID J:159523]

Chang B; Hawes NL; Hurd RE; Davisson MT; Nusinowitz S; Heckenlively JR. 2002. A point mutation in the Rpe65 gene causes retinal degeneration (rd12) in mice. (The Association for Research in Vision & Ophthalmology Annual Meeting Abstract) Invest Ophthalmol Vis Sci :3670 (Abstr.).  [MGI Ref ID J:94549]

Chang B; Hawes NL; Hurd RE; Wang J; Howell D; Davisson MT; Roderick TH; Nusinowitz S; Heckenlively JR. 2005. Mouse models of ocular diseases. Vis Neurosci 22(5):587-93. [PubMed: 16332269]  [MGI Ref ID J:156373]

Guerin K; Gregory-Evans CY; Hodges MD; Moosajee M; Mackay DS; Gregory-Evans K; Flannery JG. 2008. Systemic aminoglycoside treatment in rodent models of retinitis pigmentosa. Exp Eye Res 87(3):197-207. [PubMed: 18644591]  [MGI Ref ID J:141999]

Krebs MP; White DA; Kaushal S. 2009. Biphasic photoreceptor degeneration induced by light in a T17M rhodopsin mouse model of cone bystander damage. Invest Ophthalmol Vis Sci 50(6):2956-65. [PubMed: 19136713]  [MGI Ref ID J:154581]

Li X; Li W; Dai X; Kong F; Zheng Q; Zhou X; Lu F; Chang B; Rohrer B; Hauswirth WW; Qu J; Pang JJ. 2011. Gene therapy rescues cone structure and function in the 3-month-old rd12 mouse: a model for midcourse RPE65 leber congenital amaurosis. Invest Ophthalmol Vis Sci 52(1):7-15. [PubMed: 21169527]  [MGI Ref ID J:171546]

Pang JJ; Chang B; Hawes NL; Hurd RE; Davisson MT; Li J; Noorwez SM; Malhotra R; McDowell JH; Kaushal S; Hauswirth WW; Nusinowitz S; Thompson DA; Heckenlively JR. 2005. Retinal degeneration 12 (rd12): a new, spontaneously arising mouse model for human Leber congenital amaurosis (LCA). Mol Vis 11:152-62. [PubMed: 15765048]  [MGI Ref ID J:104924]

Pang JJ; Chang B; Heckenlively JR; Nusinowitz S; Noorwez SM; McDowell JH; Kaushal S; Timmers AM; Hauswirth WW). 2004. Gene therapy restores vision in a natural model of RPE65 Leber congenital amaurosis: The rd12 mouse (The Association for Research in Vision & Ophthalmology Annual Meeting Abstracts) Invest Ophthalmol Vis Sci :3486 (Abstr.).  [MGI Ref ID J:94351]

Sasahara M; Otani A; Oishi A; Kojima H; Yodoi Y; Kameda T; Nakamura H; Yoshimura N. 2008. Activation of bone marrow-derived microglia promotes photoreceptor survival in inherited retinal degeneration. Am J Pathol 172(6):1693-703. [PubMed: 18483210]  [MGI Ref ID J:136339]

Thompson S; Mullins RF; Philp AR; Stone EM; Mrosovsky N. 2008. Divergent phenotypes of vision and accessory visual function in mice with visual cycle dysfunction (Rpe65 rd12) or retinal degeneration (rd/rd). Invest Ophthalmol Vis Sci 49(6):2737-42. [PubMed: 18515598]  [MGI Ref ID J:137044]

Won J; Shi LY; Hicks W; Wang J; Hurd R; Naggert JK; Chang B; Nishina PM. 2011. Mouse model resources for vision research. J Ophthalmol 2011:391384. [PubMed: 21052544]  [MGI Ref ID J:166679]

Wu Y; Fishkin NE; Pande A; Pande J; Sparrow JR. 2009. Novel lipofuscin bisretinoids prominent in human retina and in a model of recessive Stargardt disease. J Biol Chem 284(30):20155-66. [PubMed: 19478335]  [MGI Ref ID J:152624]

Zheng Q; Ren Y; Tzekov R; Zhang Y; Chen B; Hou J; Zhao C; Zhu J; Zhang Y; Dai X; Ma S; Li J; Pang J; Qu J; Li W. 2012. Differential proteomics and functional research following gene therapy in a mouse model of Leber congenital amaurosis. PLoS One 7(8):e44855. [PubMed: 22953002]  [MGI Ref ID J:191645]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           A1

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $139.45Female or MaleHomozygous for Rpe65rd12  
Price per Pair (US dollars $)Pair Genotype
$278.90Homozygous for Rpe65rd12 x Homozygous for Rpe65rd12  

Standard Supply

Research Strain. Availability determined by The Jackson Laboratory scientist holding the strain.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $181.30Female or MaleHomozygous for Rpe65rd12  
Price per Pair (US dollars $)Pair Genotype
$362.60Homozygous for Rpe65rd12 x Homozygous for Rpe65rd12  

Standard Supply

Research Strain. Availability determined by The Jackson Laboratory scientist holding the strain.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Research Strain. Availability determined by The Jackson Laboratory scientist holding the strain.

General Supply Notes

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


See Terms of Use tab for General Terms and Conditions


The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
Ordering Information
JAX® Mice
Surgical and Preconditioning Services
JAX® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use


General Terms and Conditions


Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:207-288-6470

JAX® Mice, Products & Services Conditions of Use

"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"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "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 the 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 or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

No Warranty

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 mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

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 and PRODUCTS 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.


(6.5)