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   Donating Investigator Dr. Alexandra L Joyner,   Memorial Sloan-Kettering Cancer Center

Description
Mice homozygous for this Gli3^flox conditional allele are viable and fertile, with loxP sites flanking exon 8 of the targeted gene. When bred to mice that express Cre recombinase, the resulting offspring will have exon 8 deleted in the cre-expressing tissue(s). This results in a frameshift mutation upstream of the DNA-binding domain following splicing of mRNA from exon 7 to 9 and is reported to confer the null phenotype. These Gli3^flox mutant mice may be useful in generating conditional mutations for studying Hedgehog/Sonic Hedgehog signaling in the development of many organs (such as central nervous system and limb patterning), as well as the role of Gli3 in adult organs.

When bred to a strain expressing Cre recombinase in the nervous system (see Stock No. 003771 for example), this mutant mouse strain may be useful in studies of mid/hind brain development.

When bred to a strain with a En1 null allele and expressing Cre recombinase in brain (see Stock No. 007916 for example), this mutant mouse strain may be useful in studies of mid/hind brain development.

Development
A targeting vector was designed to place a loxP site and frt-flanked neo cassette upstream of exon 8, as well as a loxP site (containing an EcoRV site) downstream of exon 8 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 C57BL/6 mice. The resulting Gli3^flox-neo mice were then bred to an Flp recombinase expressing strain (on a 129S6/SvEvTac genetic background; see Stock No. 003800) to remove the frt-flanked neo cassette; thus generating Gli3^flox offspring. Mice harboring only the Gli3^flox mutation were selected and bred to / maintained on an outbred Swiss Webster genetic background 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, Gli3^flox mice were bred to 129S1/SvImJ (Stock No. 002448) for at least one generation to establish the colony.

Control Information

	Control
	Please Inquire	These mice arrived at The Jackson Laboratory on a Swiss Webster genetic background. Upon arrival, The Jackson Laboratory bred mutant mice to 129S1/SvImJ (Stock No. 002448) for at least one generation, then bred heterozygous mice together to generate the homozygous colony.
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Gli3

000026	B6.C3-Gli3Xt-J/J
001434	C3HeB/FeJ x STX/Le-Mc1rE-so Gli3Xt-J Zeb1Tw/J
001533	C3HeB/FeJ-Mc1rE-so Gli3Xt-J/J
013124	STOCK Gt(ROSA)26Sortm3(Gli3)Amc/J

View Strains carrying other alleles of Gli3     (4 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Greig Cephalopolysyndactyly Syndrome; GCPS   (GLI3) Hypothalamic Hamartomas   (GLI3) Pallister-Hall Syndrome; PHS   (GLI3) Polydactyly, Postaxial, Type A1; PAPA1   (GLI3) Polydactyly, Preaxial IV   (GLI3)

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/? Gli3^tm1Alj/Gli3^tm1Alj

        involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6   (conditional)

• nervous system phenotype
• *normal* nervous system phenotype
  • isthmus generally normal   (MGI Ref ID J:137136)
  • superior colliculus normal   (MGI Ref ID J:137136)
  • inferior colliculus normal   (MGI Ref ID J:137136)
• • abnormal brain ventricle morphology
    • expanded mesencephalic ventricle at E10.5 and E12.5   (MGI Ref ID J:137136)
  • abnormal hindbrain morphology   (MGI Ref ID J:137136)
  • • abnormal cerebellar foliation
      • abnormal at E18.5   (MGI Ref ID J:137136)
      • cerebellum otherwise normal   (MGI Ref ID J:137136)
  • abnormal rhombomere morphology
    • some Purkinje cells in anterior isthmus region   (MGI Ref ID J:137136)
    • Purkinje projections into posterior isthmus region   (MGI Ref ID J:137136)
    • dorsal mesencephalon, isthmus, and r1 not distinct at E10.5 and E12.5   (MGI Ref ID J:137136)
    • isthmus flexure less prominent   (MGI Ref ID J:137136)
    • thickness of ventricular zone increased   (MGI Ref ID J:137136)
  • abnormal tectum morphology
    • misshapen   (MGI Ref ID J:137136)
  • • enlarged tectum   (MGI Ref ID J:137136)
• embryogenesis phenotype
• abnormal rhombomere morphology
  • some Purkinje cells in anterior isthmus region   (MGI Ref ID J:137136)
  • Purkinje projections into posterior isthmus region   (MGI Ref ID J:137136)
  • dorsal mesencephalon, isthmus, and r1 not distinct at E10.5 and E12.5   (MGI Ref ID J:137136)
  • isthmus flexure less prominent   (MGI Ref ID J:137136)
  • thickness of ventricular zone increased   (MGI Ref ID J:137136)

Gli3^tm1Alj/Gli3^tm1Alj Tg(Nes-cre)1Kln/?

        involves: 129S6/SvEvTac * C57BL/6 * SJL   (conditional)

• nervous system phenotype
• *normal* nervous system phenotype
  • cerebellum normal   (MGI Ref ID J:137136)
• • abnormal rhombomere morphology
    • isthmus enlarged   (MGI Ref ID J:137136)
  • enlarged tectum   (MGI Ref ID J:137136)
• embryogenesis phenotype
• abnormal rhombomere morphology
  • isthmus enlarged   (MGI Ref ID J:137136)

View Research Applications

Research Applications

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

Developmental Biology Research
Limb Patterning Defects

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
Neurobiology Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Gli3tm1Alj
Allele Name		targeted mutation 1, Alexandra L Joyner
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Gli3F; Gli3flox;
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		Gli3, GLI-Kruppel family member GLI3
Chromosome		13
Gene Common Name(s)		ACLS; AI854843; AU023367; Bph; GCPS; GLI3-190; GLI3FL; PAP-A; PAPA; PAPA1; PAPB; PHS; PPDIV; Pdn; Xt; add; anterior digit pattern deformity; brachyphalangy; expressed sequence AI854843; expressed sequence AU023367; extra toes; polydactyly Nagoya;
Molecular Note		An frt-flanked neo cassette with a 5' loxP site was inserted upstream of exon 8 and an additional loxP site was inserted downstream of exon 8. Germ line, flp-mediated recombination was used to remove the neo cassette leaving exon 8 floxed. [MGI Ref ID J:137136]

Genotyping

Genotyping Information

Genotyping Protocols

Gli3^tm1Alj, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Blaess S; Stephen D; Joyner AL. 2008. Gli3 coordinates three-dimensional patterning and growth of the tectum and cerebellum by integrating Shh and Fgf8 signaling. Development 135(12):2093-103. [PubMed: 18480159]  [MGI Ref ID J:137136]

Additional References

Gli3^tm1Alj related

Bowers M; Eng L; Lao Z; Turnbull RK; Bao X; Riedel E; Mackem S; Joyner AL. 2012. Limb anterior-posterior polarity integrates activator and repressor functions of GLI2 as well as GLI3. Dev Biol 370(1):110-24. [PubMed: 22841643]  [MGI Ref ID J:188038]

Su CY; Bay SN; Mariani LE; Hillman MJ; Caspary T. 2012. Temporal deletion of Arl13b reveals that a mispatterned neural tube corrects cell fate over time. Development 139(21):4062-71. [PubMed: 23014696]  [MGI Ref ID J:188997]

Taniguchi K; Anderson AE; Sutherland AE; Wotton D. 2012. Loss of Tgif function causes holoprosencephaly by disrupting the SHH signaling pathway. PLoS Genet 8(2):e1002524. [PubMed: 22383895]  [MGI Ref ID J:183402]

Wang H; Ge G; Uchida Y; Luu B; Ahn S. 2011. Gli3 is required for maintenance and fate specification of cortical progenitors. J Neurosci 31(17):6440-8. [PubMed: 21525285]  [MGI Ref ID J:171423]

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 together.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Please Inquire	These mice arrived at The Jackson Laboratory on a Swiss Webster genetic background. Upon arrival, The Jackson Laboratory bred mutant mice to 129S1/SvImJ (Stock No. 002448) for at least one generation, then bred heterozygous mice together to generate the homozygous colony.
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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