Post by Dr. Juan Carlos Espinosa, researcher at the Animal Health Research Center (INIA-CISA):
The macaque has been frequently used as an animal model to assess the zoonotic potential of prion-produced diseases, especially for classical bovine spongiform encephalopathy that caused the “mad cow” disease epidemic.
The amino acid sequence of the prion protein (PrP) plays a key role in determining susceptibility to prion strains and only an amino acid change can alter this susceptibility. Therefore, in many studies of susceptibility to infection with different strains of prions have been carried out with transgenic mice that express the prion protein gene of other species (for example, bovine, sheep, swine or human). Animal models cannot be replaced because it has not been possible to establish effective cell models for studies of prion strain transmission between different species. Macaque and human PrP sequences only have nine amino acid differences, but it is unknown if these changes are related to susceptibility to infection with different prion strains.
In a study led by the Molecular and Cellular Biology group of Prions of the Center for Research in Animal Health (INIA-CISA) has compared the susceptibility of macaques and humans against different strains of prions from other species such as cows, sheep or goats. Experiments have been carried out in transgenic mice expressing the macaque and human PrP.
The results show that there are similarities in the transmission of most prion strains inoculated in the transgenic mice expressing the macaque and PrP mice. human. This suggests that the macaque is a suitable model to assess human susceptibility to most prion strains analyzed. Interestingly, mice expressing macaque PrP were more susceptible to infection by the BSE-classical strain than those expressing human PrP. Thus, it is explained why, although a limited number of macaques have been used in laboratory experiments, they have been infected very efficiently with the BSE-classical strain.
Espinosa, J.C., Comoy, E.E., Marin-Moreno, A. et al. Transgenic mouse models expressing human and macaque prion protein exhibit similar prion susceptibility on a strain-dependent manner. Scientific Reports 9, 15699 (2019) doi:10.1038/s41598-019-52155-z