Pank1-flox Mouse

Pank1, or pantothenate kinase 1, is a rate-limiting enzyme in CoA biosynthesis. CoA is an essential cofactor for intermediary metabolism, involved in processes like the tricarboxylic acid cycle, nutrient oxidation, histone acetylation, and synthesis of lipids, glycans, and haem [2].

In a cardiomyocyte-specific Pank1 deletion (cmPank1-/-) mouse model, Pank1 deletion significantly reduced PANK1 mRNA, protein, and CoA levels. During pressure overload, cmPank1-/-mice showed more ventricular dilation, exacerbated cardiac fibrosis, and significant changes in fatty acid and ketone metabolism-related metabolites, indicating Pank1's role in regulating fibrotic and metabolic processes during pressure overload [1]. In leptin-deficient mice with Pank1 deficiency, there was a reduction in hyperglycaemia and hyperinsulinaemia, along with a modification of global metabolism, suggesting Pank1's link to insulin and glucose homeostasis [3].

In conclusion, Pank1 is crucial for CoA biosynthesis, which is essential for multiple metabolic processes. Studies using gene-knockout mouse models have revealed its significance in heart function during pressure overload and in glucose and insulin homeostasis. These findings contribute to understanding related disease mechanisms such as heart failure and diabetes-related phenotypes [1,3].