Srebf2 Conditional Knockout mouse models

Cholesterol homeostasis is governed largely by Srebf2, the ortholog of human SREBF2, whose SREBP-2 precursor resides in the endoplasmic reticulum bound to SCAP, is retained by INSIG when sterol levels are high, and upon sterol depletion travels to the Golgi for S1P and S2P cleavage that liberates a basic helix-loop-helix leucine zipper fragment driving Hmgcr, Hmgcs1, Ldlr and Pcsk9 transcription. The gene also hosts miR-33a within an intron, coordinating cholesterol synthesis with repression of Abca1-dependent efflux, a coupling that a naive coding knockout would disrupt inadvertently. Germline deletion is largely embryonic lethal, so hepatocyte or macrophage conditional nulls are the practical design, and intron-preserving strategies or separate miR-33a alleles are essential when efflux is an endpoint. Cleavage-resistant or constitutive nuclear-form knockins test whether sterol sensing rather than transcriptional capacity is limiting, and Srebf1 compensates only partially at shared sterol response elements.

Srebf2 conditional knockout mice carry a floxed allele so you delete function only where Cre is active. The germline allele stays intact until you cross to a tissue specific Cre. Labs reach for this design when a global knockout is lethal, when they need adult onset loss, or when regional redundancy hides a whole body phenotype.