Why are horses resistant to brain-wasting prion diseases? Researchers investigate

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This image taken through a microscope shows the changes brought about in bovine spongiform encephalopathy, more commonly known as mad cow disease. The vacuoles – microscopic “holes” in the gray matter, gives the brain of infected cows a sponge-like appearance when tissue sections are examined in the lab. Photo: Dr Al Jenny, Public domain

Structural differences in a particular gene appear to be an important factor in the horse’s natural resistance to brain-wasting prion diseases, according to researchers.

Most people had never heard of prions until the rise of so-called mad cow disease in Britain in the late 1980s, which spread among cattle through contaminated feed. Nearly 200,000 cattle were infected in the years that followed.

The protein from which prions is known simply as the prion protein (PrP). It is found throughout the body, even in healthy animals. However, PrP found in infectious material is structured differently.

In effect, prions are misfolded proteins that are able to transmit their misfolded shape on to normal variants of the same protein.

These misfolded proteins cause fatal brain-wasting diseases in a range of animals. Prions cause disease in cheetahs, pumas, cats and minks, as well as chronic wasting disease in elk and deer.

However, prion diseases have not been reported in horses.

Sae-Young Won was joined by colleagues at Jeonbuk National University in South Korea in a study to learn more about the ability of horses to withstand prion-relate disease.

Previous studies have reported that the stability of PrP and species-specific amino acids of PrP are related to a species’ prion disease susceptibility, the researchers noted.

The horse has a distinctive amino acid, S167, that contributes to the stability of horse PrP.

However, findings from research in mice indicates that the protective effect of this horse-specific amino acid is elusive and suggests there is another factor related to the resistance to prion disease in horses.

Their research, reported in the journal Genes, suggests the answer lies in the protein-coding gene, Shadow Of Prion Protein (SPRN). They believe that the genetic and structural characteristics of the SPRN gene in horses provides protection against prion disease.

Discussing their findings, the researchers said horses have been considered a prion disease-resistant species based on the findings of previous research.

“Several studies in horses have tried to find distinctive features that may be associated with the mechanism of prion disease resistance.

“However, there is not enough research on prion family genes that can affect the susceptibility of prion disease.”

In addition, the researchers identified 12 horse-specific amino acids related to the SPRN gene that may also play a role in the resistance.

“To the best of our knowledge, this is the first report regarding the genetic and structural characteristics of the equine SPRN gene.”

Won, S.-Y.; Kim, Y.-C.; Kim, S.-K.; Jeong, B.-H. The First Report of Genetic and Structural Diversities in the SPRN Gene in the Horse, an Animal Resistant to Prion Disease. Genes 2020, 11, 39.

The study, published under a Creative Commons License, can be read here

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