These floxed mutant mice possess loxP sites flanking exon 2 of the Shh gene. This strain may be useful for generating conditional mutations in applications related to in studies of developmental defects resulting from disruption of Shh-dependent pathways.
Andrew P McMahon, University of Southern California
Mice that are homozygous for the Shhtm2Amc targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. This conditional mutant contains two loxP sites flanking exon 2 of the targeted allele. Cre-mediated recombination excises exon 2 and some surrounding intronic sequence, generating a null allele. When the conditional mutant is crossed with a ubiquitously-expressing Cre recombinase carrier to remove Shh activity in the early embryo, the resulting phenotype resembles the Shh null mutation. These conditional mutant mice may be mated to strains expressing Cre recombinase to study the effects of temporal and tissue-specific ablation of the targeted allele. This mutant mouse strain represents a model that may be useful in studies of developmental defects resulting from disruption of Shh-dependent pathways.
When bred to a strain expressing Cre recombinase under the control of a tetracycline-responsive promoter element (see Stock No. 006224, 006234, 006244) and a strain expressing a tetracycline-controlled activator protein in the lung and respiratory epithelium (see Stock No. 006225), this mutant mouse strain provides an inducible model for use in studies of hedgehog signaling in respiratory system development.
When bred to a strain with the targeted null allele (Stock No. 003318) and a strain expressing Cre recombinase in the skin and dental epithelium (Stock No. 004782), this mutant mouse strain may be useful in studies of hedgehog signaling and cell proliferation in the dental epithelium.
When bred to a strain with the targeted null allele (Stock No. 003318) and a strain expressing Cre recombinase in the mesonephric duct and its developmental derivatives (Stock No. 004692), this mutant mouse strain may be useful in studies of hedgehog signalling and cell proliferation/differentiation in mesenchymal cells of the kidney.
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 of hedgehog signaling in cortical interneurons.
The original recombinant allele contained a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter with flanking loxP sites. The PGK-Neo cassette was removed by Cre-mediated recombination in ES cells to produce the Shh conditional allele. In the Shh conditional allele, exon 2 is flanked by loxP sites. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were backcrossed to 129X1 mice. The donating investigator reports that these mice were intercrossed for 20 generations to the same and then maintained as a homozygous colony prior to arrival at The Jackson Laboratory.
A 140 SNP (single nucleotide polymorphism) panel analysis performed by The Jackson Laboratory in 2010 revealed these mice have large regions of C57BL/6-allele type regions throughout the genome. 16/140 markers were homozygous for C57BL/6-allele type on chromosome 5 (84.1-100.9-120.6 Mb), chromosome 8 (3.1-20.1 Mb and 54.1-73.2-93.1-109.9 Mb), chromosome 10 (60.1 Mb), chromosome 11 (63.5 Mb), chromosome 12 (34.6-54.3 Mb), and chromosome 16 (25.2 Mb and 64.1-84.3 Mb). Positions separated by a dash (-) indicated consecutive markers (although it is not determined if these regions are composed entirely of C57BL/6-type alleles). One marker on chromosome 16 was segregating for C57BL/6- and 129-allele type (45.1 Mb). Interestingly, the C57BL/6-allele type region on chromosome 8 contained one marker homozygous for 129-allele type at 35.0 Mb.
|Allele Name||targeted mutation 2, Andrew P McMahon|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||ShhC-NShh; ShhCo; Shhc; Shhf; Shhflox; Shhflx; Shhlox|
|Gene Symbol and Name||Shh, sonic hedgehog|
|Gene Synonym(s)||Dsh; HHG1; HLP3; HPE3; Hhg1; Hhg1; Hx; Hx; Hxl3; Hxl3; M100081; MCOPCB5; SMMCI; TPT; TPTPS; hedgehog gene 1; hemimelic extra toes; hemimelic extratoes like 3; short digits|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl<+>|
|Molecular Note||LoxP sites were inserted into intronic sequences flanking exon 2. This mutation has no effect on the normal function of this gene.|
|Mutations Made By|| |
Dr. Paula Lewis, AstraZeneca, R&D Boston
When maintaining a live colony, homozygous mice may be bred together. Coat color expected from breeding is Agouti.
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