Pdcd1lg2 Conditional Knockout mouse models

Pdcd1lg2, the mouse ortholog of human PDCD1LG2, encodes PD-L2 (B7-DC), a type I transmembrane protein whose IgV and IgC2 ectodomains engage PD-1 with roughly three-fold higher affinity than PD-L1 while also binding the repulsive guidance molecule RGMB on lung interstitial macrophages. Expression is largely restricted to dendritic cells, macrophages, and germinal center B cells and is driven by IL-4 and STAT6 rather than by the interferon gamma axis that dominates Cd274 induction, so PD-L2 shapes type 2 and tissue-resident tolerance more than interferon-driven adaptive resistance. Allele choice follows directly: conditional nulls isolate the ligand contribution of a defined myeloid or dendritic compartment, whereas ectodomain humanization is required whenever a candidate antibody or PD-1 fusion fails to cross-react with mouse protein. Because Cd274 covers much of the same receptor, single knockouts frequently look silent, so plan Cd274 compound genetics and pair the allele with tumor rejection, exhaustion reversal, or airway inflammation endpoints.

A floxed Pdcd1lg2 allele paired with Cre gives spatial control that whole body knockouts cannot offer. People use it to separate developmental roles from adult homeostasis, to model somatic mutations, and to match disease that begins in one organ.