These Ift88fl mice possess loxP sites flanking exons 4-6 of the intraflagellar transport 88 (Ift88) gene. This strain may be useful for studying ciliopathic human genetic diseases.
Bradley K. Yoder, University of Alabama at Birmingham
These Ift88fl mice possess loxP sites flanking exons 4-6 of the intraflagellar transport 88 (Ift88) gene. IFT maintain primary cilia that are present on most cell types, and mediates bidirectional movement of structural and signaling components during events such as development and wound healing. Mutations in cilia-related genes, such as Itf88, have been implicated in many ciliopathic human genetic diseases. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 4-6 deleted in cre-expressing tissues.
For example, when crossed to B6.Cg-Tg(Prrx1-cre)1Cjt/J mice (Stock No. 005584) expressing Cre recombinase in early limb bud mesenchyme, resulting offspring exhibit extensive polydactyly with loss of anteroposterior digit patterning and shortening of the proximodistal axis.
When crossed to B6;SJL-Tg(Col2a1-cre)1Bhr/J (Stock No. 003554) expressing Cre recombinase in differentiating chondrocytes, notochord and submandibular glands, resulting offspring exhibit depletion of chrondocyte cilia, premature loss of the growth plate and post-natal dwarfism.
A targeting vector was designed to insert a single loxP-site upstream of exon 4, and loxP-flanked neomycin resistance (neo) cassette downstream of exon 6 of the intraflagellar transport 88 (Ift88) gene. The construct was electroporated into 129P2/OlaHsd-derived embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a Cre expression plasmid to delete the neo cassette. Resulting ES cells contained multiple gene rearrangments; intact floxed-exons 4-6, intact floxed-neo cassette, or excision of both exons 4-6 and the neo cassette. Correctly targeted ES cells, containing only the floxed-exons, were injected into blastocysts and resulting chimeric males were bred with C57BL/6J females. Resulting offspring were bred to C57BL/6J mice for at least 6 generations to establish a colony. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Bradley K Yoder|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||Ift88fl; polarisLoxP|
|Gene Symbol and Name||Ift88, intraflagellar transport 88|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||LoxP sites were inserted to flank exons 4-6.|
When maintaining a live colony mice homozygous for the floxed allele may be bred together.
When using the Ift88fl mouse strain in a publication, please cite the originating article(s) and include JAX stock #022409 in your Materials and Methods section.