Pdgfrb Knockin 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.

Pdgfrb knockin models place a defined sequence at the endogenous locus. Expression stays under native regulation, which matters for reporters, tags, and precise allele swaps.