Strain Name:

STOCK Efna2tm1Jgf Efna5tm1Ddmo/J

Stock Number:

005992

Availability:

Repository- Live

These ephrin A2/ephrin A5 double mutant mice may be useful in studies of retinocollicular mapping, axon topography, neuron projection, and modality-specific compartmentalization of visual, auditory, and somatosensory thalamic relay pathways.

Description

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered Mutant Mice.
Mating SystemSee Colony Maintenance
Specieslaboratory mouse
GenerationN1F0 (03-SEP-08)
 
Donating Investigator David Feldhiem,   University of California at Santa Cruz

Description
Mice homozygous for both targeted mutations are viable, fertile, and normal in size. 10-20% of females homozygous at both loci neglect their litters. Double homozygous mice have no endogenous protein expression in inferior colliculus (IC) or superior colliculus (SC), and thus lack the concentration gradient created by the endogenous proteins across the midbrain in wildtype mice. Temporal and nasal retinal axon termination is severely altered: multiple ectopic aborizations in the SC indicate abnormalities in both anteroposterior and dorsoventral topography. Following surgical ablation of portions of the midbrain (including IC and SC), cross-modal innervation by retinal neurons is greater in double homozygous mutants compared to wildtype. Mice heterozygous at both loci have greater reproductive performance compared to homozygotes. Further, double heterozygotes have temporal (but not nasal) retinal axon aborization in the SC with diminished frequency and severity. These ephrin A2/ephrin A5 double mutant mice may be useful in studies of retinocollicular mapping, axon topography, neuron projection, and modality-specific compartmentalization of visual, auditory, and somatosensory thalamic relay pathways.

Development
These mice harbor two targeted mutations; ephrin A2 and ephrin A5. For the ephrin A2 targeted mutation, a targeting vector was designed to insert a neomycin cassette in exon 2 after amino acid 66 (and just upstream of a cysteine repeat motif conserved throughout the ephrin family) of the Efna2 gene. The construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Chimeric mice were bred with 129/SvEv mice. Mutant offspring were crossed to create homozygous mutant mice (Efna2-/-). The ephrin A5 targeted mutation was independently created by replacing the portion of Efna5 exon 2 encoding amino acids 42-129 with a PGK-neo cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 ES cells. Chimeric mice were bred with C57BL/6 mice. Mutant offspring were crossed to Swiss Webster mice and then made homozygous for this mutation (Efna5-/-). Double mutant mice were obtained by crossing Efna2-/- in a 129/SvEv background with a Efna5-/- in a mixed background (Swiss-Webster, C57BL/6, 129). Upon arrival at The Jackson Laboratory, double mutant mice were bred with C57BL/6J for at least one generation to establish the colony.

Control Information

  Control
   None Available
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

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

Efna2tm1Jgf/Efna2+ Efna5tm1Ddmo/Efna5+

        involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ
  • nervous system phenotype
  • abnormal sensory neuron innervation (MGI Ref ID J:61499)
    • single ectopic arborizations of temporal axons from the retina but normal nasal arborizations

Efna2tm1Jgf/Efna2tm1Jgf Efna5tm1Ddmo/Efna5tm1Ddmo

        involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ
  • nervous system phenotype
  • abnormal sensory neuron innervation (MGI Ref ID J:61499)
    • ectopic arborization of both retinal temporal axons and nasal axons are more sever than in singly homozygous mice
    • usually multiple ectopic arborizations are seen
    • normal arborization sometimes lost
View Research Applications

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

Developmental Biology Research
Internal/Organ Defects (brain)
Neurodevelopmental Defects

Neurobiology Research
Neurodevelopmental Defects

Research Tools
Neurobiology Research
Sensorineural Research

Sensorineural Research
Eye Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol Efna2tm1Jgf
Allele Name targeted mutation 1, John G Flanagan
Allele Type Targeted (knock-out)
Common Name(s) A2-; ephrin-A2-;
Strain of Origin129S6/SvEvTac
ES Cell Line NameTC-1
ES Cell Line Strain129S6/SvEvTac
Gene Symbol and Name Efna2, ephrin A2
Chromosome 10
Gene Common Name(s) Cek7-L; ELF-1; EPLG6; Ephrin-A2; Epl6; HEK7-L; LERK-6; LERK6; eph-related receptor tyrosine kinase ligand 6; ephrin A6;
Molecular Note A neomycin selection cassette, containing stop codons in all three reading frames, was inserted after the sequence encoding amino acid 66. The insertion was upstream of a conserved cysteine residue motif. RT-PCR analysis of midbrain RNA showed an absenceof transcript in homozygous mutant embryos. [MGI Ref ID J:61499]
 
Allele Symbol Efna5tm1Ddmo
Allele Name targeted mutation 1, Dennis D M O'Leary
Allele Type Targeted (knock-out)
Common Name(s) A5-; ephrin-A5-;
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line NameR1
ES Cell Line Strain(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Efna5, ephrin A5
Chromosome 17
Gene Common Name(s) AF1; AL-1; AV158822; EFL-5; EFL5; EPLG7; Ephrin-A5; Epl7; GLC1M; LERK-7; LERK7; RAGS; eph-related receptor tyrosine kinase ligand 7; expressed sequence AV158822;
Molecular Note The insertion of a neomycin selection cassette deleted sequence encoding amino acids 42 through 129 as well as a 5' splice acceptor. RT-PCR analysis showed an absence of transcript in homozygous mutant mice. [MGI Ref ID J:45896]

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)

Feldheim DA; Kim YI; Bergemann AD; Frisen J; Barbacid M; Flanagan JG. 2000. Genetic analysis of ephrin-A2 and ephrin-A5 shows their requirement in multiple aspects of retinocollicular mapping [see comments] Neuron 25(3):563-74. [PubMed: 10774725]  [MGI Ref ID J:61499]

Additional References

Efna2tm1Jgf related

Cang J; Kaneko M; Yamada J; Woods G; Stryker MP; Feldheim DA. 2005. Ephrin-as guide the formation of functional maps in the visual cortex. Neuron 48(4):577-89. [PubMed: 16301175]  [MGI Ref ID J:107593]

Cang J; Niell CM; Liu X; Pfeiffenberger C; Feldheim DA; Stryker MP. 2008. Selective disruption of one Cartesian axis of cortical maps and receptive fields by deficiency in ephrin-As and structured activity. Neuron 57(4):511-23. [PubMed: 18304481]  [MGI Ref ID J:132879]

Ellsworth CA; Lyckman AW; Feldheim DA; Flanagan JG; Sur M. 2005. Ephrin-A2 and -A5 influence patterning of normal and novel retinal projections to the thalamus: conserved mapping mechanisms in visual and auditory thalamic targets. J Comp Neurol 488(2):140-51. [PubMed: 15924339]  [MGI Ref ID J:99706]

Feng G; Laskowski MB; Feldheim DA; Wang H; Lewis R; Frisen J; Flanagan JG; Sanes JR. 2000. Roles for ephrins in positionally selective synaptogenesis between motor neurons and muscle fibers. Neuron 25(2):295-306. [PubMed: 10719886]  [MGI Ref ID J:60774]

Haustead DJ; Lukehurst SS; Clutton GT; Bartlett CA; Dunlop SA; Arrese CA; Sherrard RM; Rodger J. 2008. Functional topography and integration of the contralateral and ipsilateral retinocollicular projections of ephrin-A-/- mice. J Neurosci 28(29):7376-86. [PubMed: 18632942]  [MGI Ref ID J:139255]

Holmberg J; Armulik A; Senti KA; Edoff K; Spalding K; Momma S; Cassidy R; Flanagan JG; Frisen J. 2005. Ephrin-A2 reverse signaling negatively regulates neural progenitor proliferation and neurogenesis. Genes Dev 19(4):462-71. [PubMed: 15713841]  [MGI Ref ID J:96025]

Jiao JW; Feldheim DA; Chen DF. 2008. Ephrins as negative regulators of adult neurogenesis in diverse regions of the central nervous system. Proc Natl Acad Sci U S A 105(25):8778-83. [PubMed: 18562299]  [MGI Ref ID J:137200]

Lyckman AW; Jhaveri S; Feldheim DA; Vanderhaeghen P; Flanagan JG; Sur M. 2001. Enhanced plasticity of retinothalamic projections in an ephrin-A2/A5 double mutant. J Neurosci 21(19):7684-90. [PubMed: 11567058]  [MGI Ref ID J:71649]

Pfeiffenberger C; Cutforth T; Woods G; Yamada J; Renteria RC; Copenhagen DR; Flanagan JG; Feldheim DA. 2005. Ephrin-As and neural activity are required for eye-specific patterning during retinogeniculate mapping. Nat Neurosci 8(8):1022-7. [PubMed: 16025107]  [MGI Ref ID J:101436]

Pfeiffenberger C; Yamada J; Feldheim DA. 2006. Ephrin-As and patterned retinal activity act together in the development of topographic maps in the primary visual system. J Neurosci 26(50):12873-84. [PubMed: 17167078]  [MGI Ref ID J:116767]

Efna5tm1Ddmo related

Cang J; Kaneko M; Yamada J; Woods G; Stryker MP; Feldheim DA. 2005. Ephrin-as guide the formation of functional maps in the visual cortex. Neuron 48(4):577-89. [PubMed: 16301175]  [MGI Ref ID J:107593]

Cang J; Niell CM; Liu X; Pfeiffenberger C; Feldheim DA; Stryker MP. 2008. Selective disruption of one Cartesian axis of cortical maps and receptive fields by deficiency in ephrin-As and structured activity. Neuron 57(4):511-23. [PubMed: 18304481]  [MGI Ref ID J:132879]

Cutforth T; Moring L; Mendelsohn M; Nemes A; Shah NM; Kim MM; Frisen J; Axel R. 2003. Axonal ephrin-As and odorant receptors: coordinate determination of the olfactory sensory map. Cell 114(3):311-22. [PubMed: 12914696]  [MGI Ref ID J:101720]

Depaepe V; Suarez-Gonzalez N; Dufour A; Passante L; Gorski JA; Jones KR; Ledent C; Vanderhaeghen P. 2005. Ephrin signalling controls brain size by regulating apoptosis of neural progenitors. Nature 435(7046):1244-50. [PubMed: 15902206]  [MGI Ref ID J:99355]

Dufour A; Seibt J; Passante L; Depaepe V; Ciossek T; Frisen J; Kullander K; Flanagan JG; Polleux F; Vanderhaeghen P. 2003. Area specificity and topography of thalamocortical projections are controlled by ephrin/Eph genes. Neuron 39(3):453-65. [PubMed: 12895420]  [MGI Ref ID J:85411]

Ellsworth CA; Lyckman AW; Feldheim DA; Flanagan JG; Sur M. 2005. Ephrin-A2 and -A5 influence patterning of normal and novel retinal projections to the thalamus: conserved mapping mechanisms in visual and auditory thalamic targets. J Comp Neurol 488(2):140-51. [PubMed: 15924339]  [MGI Ref ID J:99706]

Feng G; Laskowski MB; Feldheim DA; Wang H; Lewis R; Frisen J; Flanagan JG; Sanes JR. 2000. Roles for ephrins in positionally selective synaptogenesis between motor neurons and muscle fibers. Neuron 25(2):295-306. [PubMed: 10719886]  [MGI Ref ID J:60774]

Frisen J; Yates PA; McLaughlin T; Friedman GC; O'Leary DD; Barbacid M. 1998. Ephrin-A5 (AL-1/RAGS) is essential for proper retinal axon guidance and topographic mapping in the mammalian visual system. Neuron 20(2):235-43. [PubMed: 9491985]  [MGI Ref ID J:45896]

Haustead DJ; Lukehurst SS; Clutton GT; Bartlett CA; Dunlop SA; Arrese CA; Sherrard RM; Rodger J. 2008. Functional topography and integration of the contralateral and ipsilateral retinocollicular projections of ephrin-A-/- mice. J Neurosci 28(29):7376-86. [PubMed: 18632942]  [MGI Ref ID J:139255]

Holmberg J; Clarke DL; Frisen J. 2000. Regulation of repulsion versus adhesion by different splice forms of an Eph receptor. Nature 408(6809):203-6. [PubMed: 11089974]  [MGI Ref ID J:77779]

Lyckman AW; Jhaveri S; Feldheim DA; Vanderhaeghen P; Flanagan JG; Sur M. 2001. Enhanced plasticity of retinothalamic projections in an ephrin-A2/A5 double mutant. J Neurosci 21(19):7684-90. [PubMed: 11567058]  [MGI Ref ID J:71649]

Otal R; Burgaya F; Frisen J; Soriano E; Martinez A. 2006. Ephrin-A5 modulates the topographic mapping and connectivity of commissural axons in murine hippocampus. Neuroscience 141(1):109-21. [PubMed: 16690216]  [MGI Ref ID J:110251]

Passante L; Gaspard N; Degraeve M; Frisen J; Kullander K; De Maertelaer V; Vanderhaeghen P. 2008. Temporal regulation of ephrin/Eph signalling is required for the spatial patterning of the mammalian striatum. Development 135(19):3281-90. [PubMed: 18755772]  [MGI Ref ID J:138785]

Pfeiffenberger C; Cutforth T; Woods G; Yamada J; Renteria RC; Copenhagen DR; Flanagan JG; Feldheim DA. 2005. Ephrin-As and neural activity are required for eye-specific patterning during retinogeniculate mapping. Nat Neurosci 8(8):1022-7. [PubMed: 16025107]  [MGI Ref ID J:101436]

Pfeiffenberger C; Yamada J; Feldheim DA. 2006. Ephrin-As and patterned retinal activity act together in the development of topographic maps in the primary visual system. J Neurosci 26(50):12873-84. [PubMed: 17167078]  [MGI Ref ID J:116767]

Prakash N; Vanderhaeghen P; Cohen-Cory S; Frisen J; Flanagan JG; Frostig RD. 2000. Malformation of the functional organization of somatosensory cortex in adult ephrin-A5 knock-out mice revealed by in vivo functional imaging. J Neurosci 20(15):5841-7. [PubMed: 10908626]  [MGI Ref ID J:63611]

Yabuta NH; Butler AK; Callaway EM. 2000. Laminar specificity of local circuits in barrel cortex of ephrin-A5 knockout mice. J Neurosci 20(15):RC88. [PubMed: 10899175]  [MGI Ref ID J:70429]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, double heterozygous females are bred to double homozygous males. Donating investigator indicates that females homozygous at both loci are viable and fertile, but have 10-20% frequency of neglecting litters.
Mating SystemSee above
Diet Information LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Weeks of AgePrice*GenderGenotypes Provided
Individual Mouse Price $291.90Female or MaleHeterozygous for Efna2tm1Jgf, Homozygous for Efna5tm1Ddmo
Pairs /Price*Pair Genotype
$583.80Heterozygous for Efna2tm1Jgf, Homozygous for Efna5tm1Ddmo x Heterozygous for Efna2tm1Jgf, Homozygous for Efna5tm1Ddmo
*Price(s) in US dollars ($)

Additional Supply Details

Supply Notes

Pricing for International shipping destinations View USA Canada and Mexico pricing
Weeks of AgePrice*GenderGenotypes Provided
Individual Mouse Price $379.50Female or MaleHeterozygous for Efna2tm1Jgf, Homozygous for Efna5tm1Ddmo
Pairs /Price*Pair Genotype
$759.00Heterozygous for Efna2tm1Jgf, Homozygous for Efna5tm1Ddmo x Heterozygous for Efna2tm1Jgf, Homozygous for Efna5tm1Ddmo
*Price(s) in US dollars ($)

Additional Supply Details

Supply Notes

Supply Details

Standard SupplyRepository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes

Control Information

  Control
   None Available
 
  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


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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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