This study investigates the role of sphingosine-1-phosphate receptor 3 (S1P₃) in regulating the transendothelial transport of high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Using an endothelium-specific inducible S1P₃ Knockin mouse model, researchers demonstrated that S1P₃ enhances HDL transport via a scavenger receptor class B type I (SR-BI)-dependent mechanism while inhibiting LDL transport through an SR-BI-independent pathway. These opposing effects suggest that S1P₃ plays a crucial role in maintaining endothelial barrier function and lipid homeostasis.
S1P₃ differentially regulates the transendothelial transport of HDL and LDL, promoting HDL transport via SR-BI and inhibiting LDL transport through an SR-BI-independent mechanism, highlighting its potential as a therapeutic target in atherosclerosis.
Endothelium-specific inducible S1P₃ Knockin mouse model, generated by inserting the S1pr3 cDNA into the Rosa26 locus with a LoxP-STOP-LoxP (LSL) cassette, and crossed with VE-cadherin-CreERT2 mice to achieve endothelial-specific expression upon tamoxifen induction.
Atherosclerosis, Endothelial function, Lipid metabolism, Sphingosine-1-phosphate signaling
Rosa26 Knockin, Conditional gene expression, Endothelial-specific expression, LoxP-STOP-LoxP cassette, Tamoxifen-inducible Cre system
From model design to experimental results
Tailor-made solutions adapted to scientific questions
Comprehensive dataset package
Generated with biopharma partners and in-house
Scientific follow-up and advice along the project
Collaborative approach for problem solving and development of innovative models
Breeding facilities in US and Europe
Certified health status from professional breeders