These Ihhfl/fl mice may be useful for studying chondrocyte and osteoblast proliferation and differentiation.
Beate Lanske, Harvard School of Dental Medicine
These Ihhfl/fl mutant mice possess loxP sites flanking exon 1 of the Indian hedgehog (Ihh) gene. IHH is involved in growth plate maintenance and sustaining trabecular bone after birth. It is also essential for chondrocyte proliferation and differentiation, and osteoblast differentiation during prenatal endochondral bone formation. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 1 deleted in the cre-expressing tissues.
For example, when bred to FVB-Tg(Col2a1-cre/ERT)KA3Smac/J mice (Stock No. 006774), tamoxifen induction resulted in IHH deficient mice which exhibited complete loss of the growth plate and the articular surface, leading to loss of the primary spongiosa, and to impaired bone growth after birth.
A targeting vector was designed to insert a loxP site upstream of exon 1 of the Indian hedgehog (Ihh) gene, followed by a frt-flanked neomycin resistance (neo) cassette, and a second loxP site downstream of exon 1. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were transfected with the pEF-FLP plasmid to remove the neo cassette. ES cells lacking the neo were injected into blastocysts and resulting chimeric males were bred to C57BL/6NCrl females. Progeny were crossed to remove the Flp-expressing transgene, and the donating investigator reports that the mice were bred to C57BL/6NCrl mice for at least 20 generations (see SNP note below). Upon arrival, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Four of the 27 markers throughout the genome were segregating for 129, suggesting an incomplete backcross.
|Allele Name||targeted mutation 1, Beate Lanske|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Ihh, Indian hedgehog|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A targeting vector was designed to insert a loxP site upstream of exon 1, followed by a frt-flanked neomycin resistance (neo) cassette, and a second loxP site downstream of exon 1. Flp-mediated recombination removed the neo cassette.|
When maintaining a live colony, homozygous mice may be bred together.
When using the Ihhfl mouse strain in a publication, please cite the originating article(s) and include JAX stock #024327 in your Materials and Methods section.