An arterial disease, recently discovered in cats of the Korat breed, resembles genetic familial hypercholesterolemia (FH), a cholesterol disorder in humans. Affected cats have been observed to have very high blood cholesterol levels, fatty deposits in the blood vessels and clinical symptoms, such as heart and renal failure as well as arterial thrombosis in the lower limbs.
“We identified a mutation in the LDLR gene, a key gene in the regulation of cholesterol, as a factor in atherosclerosis in Korat cats. The same gene is by far the most significant cause of FH in humans,” says Docent Marjo Hytönen of the University of Helsinki and the Folkhälsan Research Center.
In humans, the disorder is often inherited from one parent but in cats the symptoms occur only if the defective gene is inherited from both parents. Approximately one fifth of Korat cats carry the defective gene without symptoms.
“The gene discovery makes it possible to identify carriers using a genetic test, helping Korat breeders prevent the incidence of the disease,” Hytönen continues.
Evolutionary traits open up new research avenues
The feline genome brings an exciting new angle to research. As a result of evolution, cats lack another significant gene associated with cholesterol regulation, PCSK9. In humans, this gene regulates the quantity of LDL receptors in the liver. Consequently, the lack of PCSK9 has previously been thought to protect cats from arterial diseases by intensifying LDL receptor functioning and improving cholesterol elimination from the body.
“It is interesting that the absence of the PCSK9 gene did not in fact entirely protect cats from arterial disease. This creates a unique opportunity for investigating the LDL receptor defect without the effect of this gene, and it likely explains the differences in models of inheritance between humans and cats,” says Professor Hannes Lohi of the University of Helsinki and the Folkhälsan Research Center.
Boost to gene therapy from the feline model?
The LDLR gene defect identified in cats would be an excellent structural fit for gene manipulation experiments. The research group is considering cellular-level tests to fix the gene defect using genome editing techniques.
“This finding not only deepens our understanding of genetically high cholesterol levels in the blood and atherosclerosis in humans, but potentially also lays the groundwork for new courses of treatment,” Lohi sums up.
Original article
Hytönen, M. K., Karkamo, V., Hundi, S., Airas, N., Kaukonen, M., Sukura, A., Lyons, L. A., Anderson, H., Kareinen, I. & Lohi, H. (2025). A feline model of human low-density lipoprotein receptor-related atherosclerosis. Animal Genetics.