STOCK Gli2^tm2.1Alj/J

Stock number: 007922
Research areas: Developmental Biology Research, Neurobiology Research, Research Tools

Description

Mice homozygous for this Gli2^lzki allele harbor a β-galactosidase "knock-in" (lzki) mutation that also abolishes endogenous GLI-Kruppel family member GLI2 (Gli2) gene function, and may be useful for studying Hedgehog/Sonic Hedgehog signaling in the development of many organs (such as central nervous system and axis patterning), as well as the role of Gli2 in adult organs.

Detailed description

Mice homozygous for this Gli2^lzki allele harbor a β-galactosidase "knock-in" (lzki) allele that also abolishes endogenous gene function. As such, homozygous mice die at birth with many defects including absence of Sonic Hedgehog-expressing floor plate cells, reduction of Nkx2.2-expressing V3 interneurons in the spinal cord, and defects in midbrain, cerebellum and lung development. Under control of the upstream promoter/enhancer elements, lacZ expression is observed in a pattern identical to the wild-type gene. Heterozygotes are viable and fertile. These Gli2^lzki mice may be useful for studying Hedgehog/Sonic Hedgehog signaling in the development of many organs (such as central nervous system and axis patterning), as well as the role of Gli2 in adult organs.

Development

A targeting vector was designed with a nuclear localized β-galactosidase cDNA (with 1.7 kb of 3' UTR and three tandem SV40 poly A sequence repeats downstream) and followed by a reverse-oriented loxP-flanked neo cassette. This construct was used to replace a portion of the first coding exon (exon 2) of the targeted gene (including the ATG start codon) via electroporation 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 Webster outbred mice. The resulting Gli2^nlzki heterozygotes were then bred to cre expressing mice (on a Swiss Webster genetic background) to remove the neo cassette, generating Gli2^lzki offspring (with a single loxP site remaining after the SV40 polyA). These Gli2^lzki mutant mice were bred 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, Gli2^lzki mice were bred to 129S1/SvImJ (Stock No. 002448) for at least one generation to establish the colony.

Allele

Symbol: Gli2^tm2.1Alj
Name: targeted mutation 2.1, Alexandra L Joyner
MGI accession ID: MGI:2158472
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Synonyms: Gli2^lacZ; Gli2^lz; Gli2^lzki
Marker symbol: Gli2
Marker name: GLI-Kruppel family member GLI2
Marker synonyms: CJS; HPE9; PHS2; THP1; THP2
Chromosome: 1
Strain of origin: 129S6/SvEvTac
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: LacZ expression is observed in a pattern identical to the wild-type targeted gene.
Molecular note: A lacZ gene and a loxP-flanked neomycin selection cassette replaced 56 bp of exon 2, including the initiation codon. The neomycin selection cassette was removed by Cre mediated recombination in mice by crossing Gli2^tm2Alj mice with NLS-cre expressing mice, and selecting for offspring that no longer had the neomycin cassette.