Cavin1-flox Mouse

Cavin1, also known as caveolae-associated protein 1 and encoded by the polymerase I and transcript release factor (PTRF) gene, is essential for caveolae biogenesis. It functions in processes like regulating membrane tension, signaling cascades, and lipid sorting. Caveolae are small plasma membrane invaginations, and Cavin1's interaction with caveolin 1 is crucial for their formation [3,4,5].

In a study on drug-induced QT prolongation (diLQT), Cavin1 was found to regulate the susceptibility to diLQT. CAVIN1 expression levels in patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) affected the response to hERG blockers like sotalol. Higher CAVIN1 expression in more sensitive iPS-CMs led to hERG channel translocation from the membrane to the cytoskeleton-associated fractions upon sotalol treatment, reducing the delayed-rectifier potassium current (IKr) and prolonging the late repolarization phase [1].

In glioblastoma, the small-molecular inhibitor EPIC-1042 interrupted the interaction between PTRF/Cavin1 and caveolin-1, reducing small extracellular vesicles (sEVs) secretion to decrease temozolomide (TMZ) efflux and inducing PARP1 autophagic degradation, enhancing TMZ efficacy [2].

In congenital generalized lipodystrophy type 4 (CGL4), a novel pathogenic mutation of the CAVIN1/PTRF gene was found in two siblings. Cavin-1 dysfunction led to a clinical phenotype characterized by absence of adipose tissue and muscular dystrophy [3].

Cavin1 deficiency in C57BL/6J mice caused neonatal death due to disorder of hepatic glycogen metabolism, as it impaired fenestration in liver sinusoidal endothelial cells (LSECs) by inhibiting the RhoA-Rho-associated protein kinase 2-LIM domain kinase-Cofilin signaling pathway [6].

In conclusion, Cavin1 plays diverse and crucial roles in multiple biological processes and disease conditions. Its function in caveolae biogenesis has far-reaching impacts on various cellular functions. Studies using genetic models, such as gene-knockout mouse models in the case of Cavin1 deficiency, have revealed its significance in diseases like diLQT, glioblastoma, CGL4, and neonatal hypoglycemia related to hepatic glycogen metabolism disorder.