STOCK Lrp1^tm2.1Her/J

Stock number: 012604
Product name: LRP^flox
Research areas: Cardiovascular Research, Metabolism Research, Neurobiology Research, Research Tools

Description

This LRP^flox strain may be useful for studying physiological role of LRP in the uptake of cholesterol-rich lipoproteins from circulation and in maintenance of plasma lipid homeostasis.

Detailed description

These LRP^flox mutant mice possess loxP sites flanking exon 1 of the targeted low-density lipoprotein (LDL) receptor-related protein (LRP) 1 gene, Lrp1. 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, the resulting offspring will have floxed region deleted in the cre-expressing tissue, resulting in inactivation of Lrp1 gene function. This strain may be useful for studying physiological role of LRP in the uptake of cholesterol-rich lipoproteins from circulation and in maintenance of plasma lipid homeostasis.

Development

A targeting vector was designed to insert a loxP-flanked neomycin resistance (neo) cassette upstream of the 5' initiation site, and a single loxP site downstream of exon 1 of the low-density lipoprotein (LDL) receptor-related protein (LRP) 1 gene, Lrp1. [Note: the Donating Investigator provided this corrected description of the allele in July 2015. It differs from that found in Nat Biotechnol 14:1562.] The construct was electroporated into 129S7/SvEvBrd-derived JH1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to C57BL/6 to establish a colony. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Note on discovery of floxed allele components: In 2024, expanded quality control analyses by The Jackson Laboratory concluded the males sent to The Jackson Laboratory in 2010 (and our subsequent live colony and cryopreserved sperm bankstocks) have the Lrp1 floxed exon 1 allele absent of the neo sequence - i.e., loxP::exon1::loxP [without neo]. While it has not been determined if absence of the neo has any adverse effect on expression of the Lrp1 floxed exon 1 allele, we have no reports of any homozygous breeding difficulties or any lethality.

Allele

Symbol: Lrp1^tm2.1Her
Name: targeted mutation 2, Joachim Herz
MGI accession ID: MGI:7657694
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Lrp1
Marker name: low density lipoprotein receptor-related protein 1
Marker synonyms: A2mr; APOER; APR; b2b1554Clo; CD91; DDH3; IGFBP3R; IGFBP-3R; IGFBP3R1; KPA; LRP; LRP-1; LRP1A; TGFBR5
Chromosome: 10
Strain of origin: 129S7/SvEvBrd
Molecular note: A loxP-flanked PGK-neomycin selection cassette was inserted 240 bp upstream of the transcription initiation site, and a third loxP site was inserted 3' to exon 1 in intron 2. Cre-recombinase removed the PGK-neomycin selection cassette leaving the exon 1 flanked by loxP sites.