These Gli3flox mutant mice harbor loxP sites flanking exon 8 of the GLI-Kruppel family member GLI3 (Gli3) gene and 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.
Dr. Alexandra L Joyner, Memorial Sloan-Kettering Cancer Center
Mice homozygous for this Gli3flox 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 Gli3flox 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.
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 Gli3flox-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 Gli3flox offspring. Mice harboring only the Gli3flox 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, Gli3flox mice were bred to 129S1/SvImJ (Stock No. 002448) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Alexandra L Joyner|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||Gli3F; Gli3flox|
|Gene Symbol and Name||Gli3, GLI-Kruppel family member GLI3|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||An FRT site flanked neomycin resistance gene 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.|
|Mutations Made By|| |
Dr. Alexandra Joyner, Memorial Sloan-Kettering Cancer Center
When maintaining a live colony, homozygous mice may be bred together.
When using the STOCK Gli3tm1Alj/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008873 in your Materials and Methods section.