Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation ?pN1 Generation Definitions   Donating Investigator Dr. Alexandra L Joyner,   Memorial Sloan-Kettering Cancer Center

Description
Mice homozygous for the En1^flox conditional allele are viable and fertile, with loxP sites flanking the coding region of exon 2 of the targeted gene. When bred to mice that express Cre recombinase, the resulting offspring will have this region (encoding the engrailed homeodomain) deleted in the cre-expressing tissue(s). These En1^flox mice may be useful in generating conditional mutations for studying engrailed protein function in the embryonic mesencephalon and rhombomere 1, as well as developing cerebellum, limbs, somites, and skin.

Of note, these mice may also be useful in conjunction with other engrailed mutants (such as Stock No. 007912, Stock No. 007916, Stock No. 007917, Stock No. 007924, and Stock No. 007925).

Development
A targeting construct was designed to insert an frt-flanked neomycin cassette and loxP site upstream, and a loxP site downstream of the second exon of the targeted gene. This construct was electroporated into 129S6/SvEvTac-derived W4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with Black Swiss mice (to avoid rescue of the En1 mutant phenotype by the C57BL/6 background). The resulting En1^flox-neo mice were then bred to 129 mice constitutively expressing Flp recombinase (see Stock No. 003800) to remove the Frt-flanked neo cassette, generating En1^flox offspring. These En1^flox mutant mice were bred together or to Swiss Webster mice for many generations prior to arrival at The Jackson Laboratory. In addition, the donating investigator reports that although these mice harbor no additional mutant loci, they may contain incidental genetic background contributions as a result of past matings with other mutant mouse strains. Upon arrival, En1^flox mice were bred to 129S1/SvImJ (Stock No. 002448) for at least one generation to establish the colony.

Control Information

	Control
	None Available	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of En1

003343	B6.129S2-En1tm1Alj/J
002656	STOCK En1tm1Alj/J
007916	STOCK En1tm2(cre)Wrst/J
007912	STOCK En1tm2Alj/J
007917	STOCK En1tm7(cre/ESR1)Alj/J

View Strains carrying other alleles of En1     (5 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

En1^tm2(cre)Wrst/En1^tm8.1Alj

        involves: 129/Sv * Black Swiss * C57BL/6 * SJL   (conditional)

• nervous system phenotype
• abnormal cerebellum anterior vermis morphology
  • in most adult mice, mild foliation defect is observed   (MGI Ref ID J:134516)
  • fissure between anterior-most folia I/II and III either fails to form or is shallower than normal in most animals   (MGI Ref ID J:134516)
  • at E18.5, vermis may be slightly delayed in forming folia   (MGI Ref ID J:134516)
• • decreased anterior vermis size
    • overall size in some mutants is slightly reduced relative to wild-type at E18.5   (MGI Ref ID J:134516)
• abnormal inferior colliculus morphology   (MGI Ref ID J:134516)

View Research Applications

Research Applications

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

Neurobiology Research
Cre-lox System
      loxP-flanked Sequences

Research Tools
Cre-lox System
      loxP-flanked Sequences
Developmental Biology Research
      Cre-lox System
Genetics Research
      Mutagenesis and Transgenesis
      Mutagenesis and Transgenesis: Cre-lox System

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		En1tm8.1Alj
Allele Name		targeted mutation 8.1, Alexandra L Joyner
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		En1flox;
Mutation Made By		Dr. Alexandra Joyner,   Memorial Sloan-Kettering Cancer Center
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		W4
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		En1, engrailed 1
Chromosome		1
Gene Common Name(s)		En-1; Mo-en.1; engrailed-1;
Molecular Note		A targeting construct was designed to insert an frt-flanked neomycin cassette and loxP site upstream, and a loxP site downstream of the second exon of the targeted gene. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with Black Swiss mice (to avoid rescue of the En1 mutant phenotype by the C57BL/6 background). The resulting En1flox-neo mice were then bred to 129 mice constitutively expressing Flp recombinase to remove the Frt-flanked neo cassette, generating En1flox offspring. [MGI Ref ID J:134516]

Genotyping

Genotyping Information

Genotyping Protocols

En1^tm8.1Alj, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Sgaier SK; Lao Z; Villanueva MP; Berenshteyn F; Stephen D; Turnbull RK; Joyner AL. 2007. Genetic subdivision of the tectum and cerebellum into functionally related regions based on differential sensitivity to engrailed proteins. Development 134(12):2325-35. [PubMed: 17537797]  [MGI Ref ID J:134516]

Additional References

En1^tm8.1Alj related

Cheng Y; Sudarov A; Szulc KU; Sgaier SK; Stephen D; Turnbull DH; Joyner AL. 2010. The Engrailed homeobox genes determine the different foliation patterns in the vermis and hemispheres of the mammalian cerebellum. Development 137(3):519-29. [PubMed: 20081196]  [MGI Ref ID J:156169]

Ellisor D; Rieser C; Voelcker B; Machan JT; Zervas M. 2012. Genetic dissection of midbrain dopamine neuron development in vivo. Dev Biol 372(2):249-62. [PubMed: 23041116]  [MGI Ref ID J:190919]

Fox SR; Deneris ES. 2012. Engrailed is required in maturing serotonin neurons to regulate the cytoarchitecture and survival of the dorsal raphe nucleus. J Neurosci 32(23):7832-42. [PubMed: 22674259]  [MGI Ref ID J:185187]

Orvis GD; Hartzell AL; Smith JB; Barraza LH; Wilson SL; Szulc KU; Turnbull DH; Joyner AL. 2012. The engrailed homeobox genes are required in multiple cell lineages to coordinate sequential formation of fissures and growth of the cerebellum. Dev Biol 367(1):25-39. [PubMed: 22564796]  [MGI Ref ID J:185802]

Sillitoe RV; Stephen D; Lao Z; Joyner AL. 2008. Engrailed homeobox genes determine the organization of Purkinje cell sagittal stripe gene expression in the adult cerebellum. J Neurosci 28(47):12150-62. [PubMed: 19020009]  [MGI Ref ID J:142371]

Sillitoe RV; Vogel MW; Joyner AL. 2010. Engrailed homeobox genes regulate establishment of the cerebellar afferent circuit map. J Neurosci 30(30):10015-24. [PubMed: 20668186]  [MGI Ref ID J:162855]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	None Available	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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