Heterozygous inhibition in prion infection: the stone fence model.
The human PrP gene (PRNP) has two major polymorphic codons: 129 for methionine (M) or valine (V) and 219 for glutamate (E) or lysine (K). The PRNP heterozygotes appear to be protected from sporadic CJD compared to the PRNP homozygotes. The molecular mechanism responsible for these protective effects of PRNP heterozygosity has remained elusive. In this review, we describe the inhibition of PrP conversion observed in a series of transmission studies using PRNP heterozygous animal models. In vCJD infection, the conversion incompetent human PrP 129V molecules showed an inhibitory effect on the conversion of human PrP 129M molecules in the 129M/V heterozygous mice. Furthermore, though the human PrP 219E and PrP 219K were both conversion competent in vCJD infection, these conversion competent PrP molecules showed an inhibitory effect in the 219E/K heterozygous animals. To explain this heterozygous inhibition, we propose a possible mechanism designated as the stone fence model.
Division of CJD Science and Technology, Department of Prion Research, Tohoku University Graduate School of Medicine, Sendai, Japan.
Atsushi
A
Kobayashi
Masaki
M
Hizume
Kenta
K
Teruya
Shirou
S
Mohri
Tetsuyuki
T
Kitamoto
D000818:Animals; D004195:Disease Models, Animal; D055879:Gene Knock-In Techniques; D006579:Heterozygote; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011110:Polymorphism, Genetic; D017096:Prion Diseases / Q000235:genetics*; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics* / Q000378:metabolism
C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions