The PDGFRβ^(S)J conditional knockin allele has the endogenous PDGFRβ sequences replaced with a loxP-flanked PGKneo (lox-stop-lox) cassette upstream of the constitutively active PDGFRβJ mutant isoform (V536A mutation in the juxtamembrane domain disrupts a highly conserved juxtamembrane region in type III receptor tyrosine kinases that contacts the kinase domain important for full auto-inhibition, leading to constitutive PDGFRβ activity). Prior to Cre recombinase exposure, no expression of the constitutively active βJ mutant isoform is observed, and the mutant allele functions as a knockout. Mice homozygous for the PDGFRβ^(S)J allele are neonatal lethal. Heterozygous PDGFRβ^(S)J mice are viable and fertile with no reported abnormalities. Following Cre recombinase-mediated excision of the floxed-STOP cassette, high basal kinase activity without the addition of ligand is observed in the cre-expressing tissues.

Of note, pan-deletion of the floxed-STOP cassette can be achieved by breeding PDGFRβ^(S)J conditional knockin mice with mice expressing Cre recombinase in early embryonic development (Meox2-Cre [Stock No. 003755], Sox2-Cre [Stock No. 004783], or Prm-Cre [Stock No. 003328]). In the resulting double mutant offspring, widespread expression of the constitutively active PDGFRβ leads to normal embryonic development but eventual death by ~14 days of age. In these double mutant mice, constitutively active PDGFRβ induces a battery of immune response genes in pericytes and mesenchymal cells, and also inhibits in vitro differentiation of white adipocytes.

When PDGFRβ^(S)J conditional knockin mice are bred to Sm22-Cre mice [Stock No. 004746], constitutively active PDGFRβ drives cell proliferation and downregulates differentiation genes in aortic vascular smooth muscle tissues of the double mutant offspring.

Importantly, the donating investigator reports they have not observed any consistent phenotypic differences between the Cre recombinase-activated phenotypes of PDGFRβJ and PDGFRβK (see Stock No. 018435) mice, regardless of Cre recombinase tissue specificity.