Pdgfrb Conditional Knockout mouse models

Signaling in the mural cell compartment depends on Pdgfrb, the mouse ortholog of human PDGFRB, a class III receptor tyrosine kinase activated by PDGF-B and PDGF-D that recruits PI3K, SHP2, and RAS-ERK effectors and is indispensable for pericyte and vascular smooth muscle recruitment to developing endothelium. Human disease spans both directions of dosage: gain-of-function substitutions in infantile myofibromatosis and Kosaki overgrowth syndrome, COL1A1-PDGFB rearrangement in dermatofibrosarcoma protuberans, ETV6-PDGFRB fusions in eosinophilia-associated myeloid neoplasms, and loss-of-function alleles causing primary familial brain calcification with blood brain barrier failure. Germline nulls die perinatally from pericyte deficiency, glomerular defects, and hemorrhage, so conditional deletion with Pdgfrb-cre, Cspg4-cre, or Myh11-cre is required for adult vascular and fibrosis endpoints, while precise activating knockins reproduce myofibromatosis and inhibitor sensitivity. Pdgfra shares ligands and can heterodimerize, so compound alleles clarify mesenchymal redundancy; match allele class to whether the readout is barrier integrity, fibrosis, or tumor response.

Tissue restricted knockout of Pdgfrb keeps wild type function everywhere else. Breeding is often more robust, and the setup mirrors patient biology where mutations arise in a subset of cells.