Lrp6f floxed mice may be useful for studying the regulation of development through the Wnt/beta-catenin signaling cascade.
Bart O Williams, Van Andel Research Institute
Lrp6f floxed mice possess loxP sites flanking exon 2 of the low density lipoprotein receptor-related protein 6 (Lrp6) gene. LRP6 is transmembrane cell surface protein that functions as a co-receptor with Frizzled. LRP6 transmits signaling through the canonical Wnt/beta-catenin signaling cascade and plays a pivotal role in development as it is essential for cell differentiation, proliferation, and migration, as well as the development of some types of cancers. Homozygotes are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 2 deleted in the cre-expressing tissues.
When bred with B6.129X1-Twist2tm1.1(cre)Dor/J mice (Stock No. 008712) expressing Cre Recombinase in early mesenchyme, which contain precursors for the skeletal tissues, offspring exhibit only a slight delay in ossification of the skull at E17.5.
When bred to mice carrying a floxed Lrp5 allele (Stock No. 026269), and subsequently bred to B6.129X1-Twist2tm1.1(cre)Dor/J mice, double knockout mice die shortly after birth, exhibiting abnormalities including reduced body size, misshaped skull and limbs.
A targeting vector was designed to insert a loxP site upstream of exon 2, and a frt-flanked neomycin resistance (neo) cassette, in reverse orientation, followed by a second loxP site downstream of exon 2 of the low density lipoprotein receptor-related protein 6 (Lrp6) gene. The construct was electroporated into 129S1/Sv-Oca2+ Tyr+ Kitl+-derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. Resulting chimeric mice were bred with 129S4/SvJaeSor-Gt(ROSA)26Sortm1(FLP1)Dym/J transgenic mice (Stock No. 003946) to delete the neo cassette, and progeny were crossed to remove the Flp-expressing transgene. Mice were maintained on a mixed B6 x 129 background. Upon arrival, Lrp6f mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1.1, van Andel Research Institute|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Lrp6, low density lipoprotein receptor-related protein 6|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||A loxP site was inserted upstream of exon 2. An FRT-flanked neo cassette with a 5' loxP site was inserted downstream of exon 2. Flp-mediated recombination removed the neo cassette and left exon 2 floxed.|
When maintaining a live colony, homozygous mice may be bred together.
When using the Lrp6f mouse strain in a publication, please cite the originating article(s) and include JAX stock #026267 in your Materials and Methods section.