Notably, mice expressing only PrP V127 were completely resistant to all prion strains, demonstrating a different molecular mechanism to M129V, which provides its relative protection against classical CJD and kuru in the heterozygous state.
An important determinant for CJD risk and phenotype is the M129V polymorphism of the human prion protein gene (PRNP), but there are also other coding and non-coding polymorphisms inside this gene.
The polymorphism at codon 129 (M129V) of the prion protein gene (PRNP) is a recognized genetic marker for susceptibility to Creutzfeldt-Jakob disease (CJD) in the Caucasians.
A total of 616 chromosomes from control individuals of all major continental groups, and six individuals affected by either Creutzfeldt-Jakob disease (CJD) or fatal familial insomnia (FFI), were typed with a new single-reaction protocol method and were also sequenced, with total reproducibility to screen variation at important positions (385A>G: M129V and 655G>A: E219K) in the human prion protein gene (PRNP).
FFI and a familial type of Creutzfeldt-Jakob disease (CJD178), share the D178N mutation in the PrP gene but have distinct phenotypes linked to codon 129, the site of a methionine/valine polymorphism (129M/V).