Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator David Garbers,   U.T. Southwestern Medical Center

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (protein) is detected by Western blot analysis of eye tissue. Progressive loss of electroretinograms (ERGs) of cone cells from homozygotes begins at age 3 to 5 weeks. ERGs are completely lost in mice older than 8 weeks of age. Histological analysis of mutants between 4 and 5 weeks of age reveals retinal cone cell atrophy and a reduction in the number of cone cells. Isolated retinal rod cells exhibit reduced a-wave and b-wave ERGs, and impaired photoresponse. This mutant mouse strain may be useful in studies of incomplete achromatopsia, progressive cone-rod dystrophy, retinitis pigmentosa and Leber congenital amaurosis.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt part of exon 5. The construct was electroporated into 129S6/SvEvTac derived SM1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice. Heterozygotes were bred to generate homozygotes.

Control Information

	Control
	Wild-type from the colony
	101043 B6129SF1/J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Gucy2e^tm1Gar/Gucy2e^tm1Gar

        involves: 129S6/SvEvTac * C57BL/6

• vision/eye phenotype
• abnormal eye electrophysiology (MGI Ref ID J:77627)
  • by 1 month of age, electroretinograms (ERG) of mutant mice are abnormal
• abnormal cone electrophysiology (MGI Ref ID J:77627)
  • at one month of age, cone responses to flashes in rod-saturating background are barely detectable
• abnormal rod electrophysiology (MGI Ref ID J:77627)
  • rod a-wave and b-wave of ERG are severely reduced at one month of age
  • flash response from a rod demonstrates increased time-to-peak before decaying more rapidly than in controls; rods have a higher sensitivity than wild-type
  • rods show oscillations during and after recovery from a light flash
• decreased retinal cone cell number (MGI Ref ID J:77627)
  • by 5 weeks of age, number of identifiable cones is dramatically reduced
• retinal cone cell degeneration (MGI Ref ID J:77627)
  • cells degenerate rapidly at 4-5 weeks of age, with few surviving at late stages
• nervous system phenotype
• decreased retinal cone cell number (MGI Ref ID J:77627)
  • by 5 weeks of age, number of identifiable cones is dramatically reduced
• retinal cone cell degeneration (MGI Ref ID J:77627)
  • cells degenerate rapidly at 4-5 weeks of age, with few surviving at late stages

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Gucy2e^tm1Gar/Gucy2e^tm1Gar

        involves: 129S6/SvEvTac

• vision/eye phenotype
• abnormal eye physiology (MGI Ref ID J:120903)
  • sensitivity of rods to light (half-saturating flash intensity of 13.6 photons/um²) is 3.5-fold higher than wild-type
• abnormal eye electrophysiology (MGI Ref ID J:120903)
• abnormal rod electrophysiology (MGI Ref ID J:120903)
  • scotopic a- and b-wave amplitudes in 4-6 week old mice are significantly reduced compared to wild-type responses
  • after exposure to high intensity light, followed by 1 hour of dark adaptation, a-wave amplitude recovery is delayed relative to wild-type, with only 30% recovery
• abnormal retinal cone cell morphology (MGI Ref ID J:120903)
  • at distal connecting cilia, membrane components are partitioned into layered stacks
• abnormal retinal cone cell inner segment morphology (MGI Ref ID J:120903)
  • apical inner segments of cones appear retracted from connecting cilia and surrounded by extracellular blebs
• abnormal retinal cone cell outer segment morphology (MGI Ref ID J:120903)
  • at 2 months of age, cone outer segments (COS) in retinas are extremely disorganized
• retinal degeneration (MGI Ref ID J:120903)
  • in severely degenerated cases, membranes are detached
• nervous system phenotype
• abnormal retinal cone cell morphology (MGI Ref ID J:120903)
  • at distal connecting cilia, membrane components are partitioned into layered stacks
• abnormal retinal cone cell inner segment morphology (MGI Ref ID J:120903)
  • apical inner segments of cones appear retracted from connecting cilia and surrounded by extracellular blebs
• abnormal retinal cone cell outer segment morphology (MGI Ref ID J:120903)
  • at 2 months of age, cone outer segments (COS) in retinas are extremely disorganized

View Research Applications

Research Applications

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

Gucy2e^tm1Gar related

Research Tools
Sensorineural Research (retinal degeneration)

Sensorineural Research
Eye Defects
Retinal Degeneration (retinitis pigmentosa)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Gucy2etm1Gar
Allele Name		targeted mutation 1, David L Garbers
Allele Type		Targeted (knock-out)
Common Name(s)		GC-E -; GC1 KO;
Mutation Made By		Janette Tubb,   UTSouthwestern Medical Center
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		SM1
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Gucy2e, guanylate cyclase 2e
Chromosome		11
Gene Common Name(s)		BC020186; CORD5; CORD6; CYGD; GC-E; GC1; GUC1A4; GUC2D; LCA; LCA1; RETGC-1; ROS-GC1; cDNA sequence BC020186; retGC;
Molecular Note		A neomycin selection cassette replaced the 3' portion of exon 5 encoding the transmembrane domain. Western blot analysis of protein extracts obtained from eyecups showed an absence of encoded protein in homozygous mice. [MGI Ref ID J:77627]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Yang RB; Robinson SW; Xiong WH; Yau KW; Birch DG; Garbers DL. 1999. Disruption of a retinal guanylyl cyclase gene leads to cone-specific dystrophy and paradoxical rod behavior. J Neurosci 19(14):5889-97. [PubMed: 10407028]  [MGI Ref ID J:77627]

Additional References

Gucy2e^tm1Gar related

Baehr W; Karan S; Maeda T; Luo DG; Li S; Bronson JD; Watt CB; Yau KW; Frederick JM; Palczewski K. 2007. The function of guanylate cyclase 1 and guanylate cyclase 2 in rod and cone photoreceptors. J Biol Chem 282(12):8837-47. [PubMed: 17255100]  [MGI Ref ID J:120903]

Coleman JE; Semple-Rowland SL. 2005. GC1 deletion prevents light-dependent arrestin translocation in mouse cone photoreceptor cells. Invest Ophthalmol Vis Sci 46(1):12-6. [PubMed: 15623748]  [MGI Ref ID J:95810]

Coleman JE; Zhang Y; Brown GA; Semple-Rowland SL. 2004. Cone cell survival and downregulation of GCAP1 protein in the retinas of GC1 knockout mice. Invest Ophthalmol Vis Sci 45(10):3397-403. [PubMed: 15452041]  [MGI Ref ID J:93453]

Haire SE; Pang J; Boye SL; Sokal I; Craft CM; Palczewski K; Hauswirth WW; Semple-Rowland SL. 2006. Light-driven cone arrestin translocation in cones of postnatal guanylate cyclase-1 knockout mouse retina treated with AAV-GC1. Invest Ophthalmol Vis Sci 47(9):3745-53. [PubMed: 16936082]  [MGI Ref ID J:116276]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	This strain originated on a B6;129S6 background. When held in a live colony, it was maintained by homozygous matings on the same background.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	101043 B6129SF1/J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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.

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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.