These floxed Pkd1 (polycystic kidney disease 1 homolog) mutant mice may be useful in generating conditional mutations for studies of polycystic kidney disease.
Gregory Germino, Johns Hopkins University School of Medic
These mice possess loxP sites on either side of exons 2 through 4 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 2 through 4 deleted in the cre-expressing tissue(s).
For example, when crossed to a strain with widespread Cre recombinase expression (see Stock No. 003553), this mutant mouse strain may be useful in studies of polycystic kidneys.
When bred to mice carrying Gt(ROSA)26Sortm1(cre/ERT)Nat (Stock No. 004847), tamoxifen-induced Cre-mediated recombination results in increased kidney weight.
A targeting vector containing a FRT-site flanked neo cassette and a loxP site was utilized in the construction of this mutant. This selection cassette was inserted upstream of exon 2 of the targeted gene, and another loxP site was inserted upstream of exon 4. This construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The mice were then crossed to a FLP recombinase expressing strain, on a congenic C57BL/6J background, to remove the selection cassette. Mice that had successfully undergone FLP recombination and no longer retained the cassette but did retain the loxP-flanked exons 2-4 were then backcrossed to C57BL/6 for 12 generations (see SNP note below). Heterozygotes were crossed to generate homozygotes. Upon arrival at The Jackson Laboratory the mice were crossed to C57BL/6J at least once 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. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, at least 1 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 2, Gregory G Germino|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||Pkd1cond; Pkd1flox|
|Gene Symbol and Name||Pkd1, polycystin 1, transient receptor poteintial channel interacting|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A neomycin cassette flanked by FRT sites and a single loxP site at the 3' end was inserted into intron 1. Another loxP site was inserted into intron 4 in the same orientation such that exons 2-4 could be removed upon expression of cre recombinase.|
|Mutations Made By|| |
Gregory Germino, Johns Hopkins University School of Medic
When maintaining a live colony, these mice can be bred as homozygotes.
When using the B6.129S4-Pkd1tm2Ggg/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #010671 in your Materials and Methods section.
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