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Genes & Alleles

Efna2;   Efna2tm1Jgf;   Efna5;   Efna5tm1Ddmo;

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Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Stock Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Targeted Mutation Species laboratory mouse Donating Investigator David Feldhiem,   University of California at Santa Cruz

Strain 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.

Strain 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.

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

Gene & Allele Details

Allele Symbol		Efna2tm1Jgf
Allele Name		targeted mutation 1, John G Flanagan
Common Name(s)		ephrin-A2-;
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TC-1
ES Cell Line Strain		129S6/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
Common Name(s)		ephrin-A5-/-;
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
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]

Colony Maintenance

Breeding & Husbandry	When 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.

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

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

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Price and Supply Information

Strain Name:	STOCK Efna2tm1Jgf Efna5tm1Ddmo/J
Stock Number:	005992

 

This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date:

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

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Supply Details

Standard Supply	Under Development for Distribution Colony
Supply Notes	This strain is included in the Induced Mutant Resource Colony collection.
Licensing	See General Terms and Conditions below

General Terms and Conditions

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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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