These Ihh knock-out mice exhibit embryonic lethality that may be due to circulatory abnormalities.
Andrew P McMahon, University of Southern California
Mice that are heterozygous for the targeted allele are viable and fertile. Mice homozygous for this mutation have a lethal phenotype. Half of homozygous null mice have an embryonic lethal phenotype, dying between 10.5 to 12.5 days post coitum. The cause of embryonic death may be due to circulatory abnormalities. Embryonic death also occurred in late gestation, with the remaining homozygous mutants dying at birth, due to respiratory failure. At 12.5 dpc, initial cartilaginous primordia of mutant embryos forelimbs are not abnormal, but by 13.5 dpc, mutant embryos display severe foreshortening of the forelimbs. At birth, the length of long bones of mutant animals are only one third the length of long bones of wildtype animals. Mutants have reduced chondrocyte proliferation, abnormal chondrocyte maturation and absence of mature osteoblasts in endochondral bones. Recent studies have linked mutations of Ihh to brachydactyly type A-1 St-Jacques. This mutant mouse strain represents a model that may be useful in studies of skeletal morphogenesis.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to replace the entire first exon, encoding much of the signaling peptide, and approximately 1kb of flanking sequence. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 derived blastocysts. The resulting chimeric animals were backcrossed to 129X1 mice.
|Allele Name||targeted mutation 1, Andrew P McMahon|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Ihh-; Ihhn|
|Gene Symbol and Name||Ihh, Indian hedgehog|
|Gene Synonym(s)||BDA1; HHG2|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl<+>|
|Molecular Note||A neomycin resistance cassette replaced the entire first exon, which encodes much of the signaling peptide, and approximately 1kb of flanking sequence.|
|Mutations Made By|| |
Andrew McMahon, University of Southern California
This strain originated and is maintained on a 129 background. The strain is maintained by heterozygous intercrosses. Homozygous lethal.
When using the Ihh KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004290 in your Materials and Methods section.
|Heterozygous or Wild-type for Ihh<tm1Amc>|
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