Pparg Conditional Knockout mouse models

Adipocyte identity depends on Pparg, the mouse ortholog of PPARG, a ligand-activated nuclear receptor that heterodimerizes with RXR alpha and occupies PPRE elements through tandem zinc fingers, while its ligand-binding domain accommodates fatty acid derivatives and thiazolidinediones and exchanges NCoR corepressor for coactivators upon agonist binding. Insulin sensitization additionally depends on blocking CDK5 and ERK phosphorylation of Ser273, which reprograms rather than simply activates the receptor. The PPARG2 isoform, carrying an extra amino-terminal segment from an upstream promoter, is adipose-restricted, so isoform-specific alleles ask different questions than pan-locus deletion. Germline null is embryonic lethal from placental vascular failure, making adipocyte, macrophage or intestinal conditional nulls mandatory, while dominant-negative knockins such as P467L reproduce familial partial lipodystrophy and Ser273 phospho-dead alleles isolate the antidiabetic mechanism. Ppara and Ppard bind overlapping ligands but cannot restore adipogenesis, so compensation is confined to lipid oxidation endpoints.

Conditional deletion of Pparg limits the genetic change to the lineage you choose. That helps in oncology, immunology, and metabolic work where systemic loss would muddy the read. After you confirm Cre specificity, crossing to Pparg floxed stock yields usable cohorts.