LPL CRISPR Activation Plasmid (m): sc-421460-ACT

Mouse Lpl encodes lipoprotein lipase (LPL), a secreted, heparan sulfate–binding enzyme that hydrolyzes triglycerides in circulating chylomicrons and VLDL to liberate fatty acids for uptake by adipose tissue, heart, and skeletal muscle. LPL activity is coordinated by endothelial transport and anchoring factors such as GPIHBP1 and is modulated by apolipoproteins and angiopoietin-like proteins, linking nutrient status to lipid partitioning. Through regulation of lipid uptake and storage, LPL contributes to energy homeostasis, adipocyte biology, and insulin sensitivity, and its dysregulation is associated with hypertriglyceridemia, hepatic steatosis, and atherosclerosis-related phenotypes in metabolic disease models. These features make Lpl a central node for studying lipoprotein metabolism, vascular lipid handling, and inflammation-adjacent metabolic pathways in mouse systems.

LPL CRISPR Activation Plasmid (m) provides a targeted, non-destructive approach to upregulating endogenous Lpl expression without altering the underlying DNA sequence.

LPL CRISPR Activation Plasmid (m) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the Lpl locus in human cell lines. The system is built around a catalytically inactive Cas9 (dCas9) carrying two inactivating mutations (D10A and N863A) that eliminate nuclease activity while preserving DNA binding. This dCas9 is fused to VP64, a potent transcriptional activator, and is co-expressed with a blasticidin resistance gene for selection. The second plasmid encodes the MS2-p65-HSF1 fusion protein, a secondary activator complex that works in concert with dCas9-VP64, alongside a hygromycin resistance gene. The third plasmid encodes a target-specific 20 nt sgRNA fused to two MS2 RNA aptamers that recruit the MS2-p65-HSF1 complex to the activation site, accompanied by a puromycin resistance gene. The three plasmids are delivered at a 1:1:1 mass ratio for balanced expression of all system components.

Once assembled at the target locus, the SAM complex binds within approximately 200 bp upstream of the Lpl transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous LPL expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native Lpl locus and enabling the study of LPL-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of LPL pathway restoration in tumor cells with silenced or reduced Lpl expression.

For Research Use Only. Not Intended for Diagnostic or Therapeutic Use.