Lrp6 Conditional Knockout mouse models

Sharing architecture with Lrp5, Lrp6 is the mouse ortholog of human LRP6 and encodes the more broadly required Wnt co-receptor, using its four beta-propeller and EGF repeat modules to engage Wnt ligands alongside Frizzled and its PPPSPXS-containing tail to recruit Axin after CK1gamma and Gsk3 phosphorylation, thereby stabilizing beta-catenin; Dkk1 and Sost bind the amino-terminal propellers, and Mesd chaperones folding during biosynthesis. Homozygous nulls die at or before birth with caudal truncation, neural tube closure defects, and limb abnormalities that phenocopy combined Wnt deficiencies, while the hypomorphic ringelschwanz allele survives with axial skeletal defects, so conditional deletion is the practical route for postnatal bone, metabolic, and tumor studies. Phosphomimetic tail knockins ask whether constitutive Axin capture drives signaling, antagonist-resistant propeller mutants test the Dkk1 axis genetically, and humanization supports antibody development. Because Lrp5 partially compensates in bone, plan compound conditional genetics with a skeletal or intestinal driver.

Lrp6 conditional knockout mice carry a floxed allele so you delete function only where Cre is active. The germline allele stays intact until you cross to a tissue specific Cre. Labs reach for this design when a global knockout is lethal, when they need adult onset loss, or when regional redundancy hides a whole body phenotype.