These Lrp5 (low density lipoprotein receptor-related protein 5) targeted mutation mice carry a G170V amino acid mutation that is equivalent to the G171V missense mutation reported in human patients with high bone mass. In addition, a floxed neomycin cassette insertion was used to create a hypomorphic allele. This strain may be useful in studies of bone development and homeostasis.
Matthew Warman, Children's Hospital of Boston/HHMIRead More +
These Lrp5 (low density lipoprotein receptor-related protein 5) targeted mutation mice carry a G170V amino acid mutation that is equivalent to the G171V missense mutation reported in human patients with high bone mass. A floxed neomycin cassette was placed in intron 2 in reverse transcriptional orientation to interfere with transcription of the targeted gene and create a hypomorphic allele. Expression of the mutant protein is detectable in whole femur mRNA at substantially reduced levels as compared to those of wildtype mice. Heterozygotes have bone mass comparable to that of wildtype mice. Cre-recombinase-mediated deletion of the floxed neomycin cassette restores Lrp5 expression to wildtype levels and produces the high bone mass phenotype seen in Stock No. 012669. This strain may be useful in studies of bone development and homeostasis, particularly when conditional activation of the allele in a cell type-specific manner is desired.
When bred to a strain expressing Cre recombinase in the early limb bud mesenchyme (see Stock No. 005584 for example), this mutant mouse strain may be useful in studies of bone mass regulation.
When crossed to B6N.FVB-Tg(Dmp1-cre)1Jqfe/BwdJ (see Stock No. 023047) Cre recombinase expression in odontoblasts and osteocytes, results in offspring that exhibit increased bone mass.
Glycine 170 of the targeted gene was converted to valine (equivalent to the human G171V missense mutation) via site-directed mutagenesis and a floxed neomycin selection cassette was placed in reverse transcriptional orientation in intron 2. The mutations was created in (129X1/SvJ x 129S1/Sv)F1- Kitl+-derived R1 embryonic stem (ES) cells. This strain was minimally backcrossed to C57BL/6 by the donating laboratory.
|Allele Name||targeted mutation 1, Matthew Warman|
|Allele Type||Targeted (Humanized sequence)|
|Allele Synonym(s)||GN; Lrp5 G171V-Neo|
|Gene Symbol and Name||Lrp5, low density lipoprotein receptor-related protein 5|
|Gene Synonym(s)||BMND1; EVR1; EVR4; HBM; LR3; LRP-5; LRP7; OPPG; OPS; OPTA1; VBCH2|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl<+>|
|Molecular Note||lycine 170 of the targeted gene was converted to valine (equivalent to the human G171V missense mutation) via site-directed mutagenesis and a floxed neomycin selection cassette was placed in reverse transcriptional orientation in intron 2.|
When maintained as a live colony, heterozygous or homozygous mice may be bred. Homozygotes are reportedly born at expected Mendelian frequencies. Cranial nerve and blood vessel compression due to excessive bone development may be problematic in older homozygotes.
|Please inquire about possible genotypes.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
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