Within humans, we know that prion codon 129 polymorphism (either Methionine (M) or Valine (V)) predisposes individuals to CJD. The distribution of the polymorphism in the Caucasian population is:

• 12% V/V,
• 37% M/M,
• 51% M/V

• 69% V/V,
• 25% M/M,
• 6% M/V

• 50% V/V,
• 31% M/M,
• 19% M/V

Thus heterozygosity at codon 129 (M/V) or homozygosity for V (V/V) may protect individuals from CJD . The M129 in bovine PrP^Sc probably favours interaction between the bovine protein and human PrP M129 thus allowing the interaction of the two proteins from different species and the conversion of human PrP M129 to human PrP^Sc M129
Since sheep scrapie PrP^Sc M129 does not appear to be transmitted to humans, additional species barriers exist other than those associated with PrP sequences .

Human PrP V129 protects mice from BSE but not CJD. Transgenic mice (mPrP M129) with a human transgene (hPrP V129) develop prion disease when injected with an isolate of human prions from a CJD case
Mice producing only hPrP V129 (no mPrP produced by breeding PrP null mice with human PrP V129 mice) developed disease with a much shorter incubation time. Thus the heterozygosity of mouse M129 with human V129 in the first test delayed the onset of CJD in mice the homozygosity for hPrP V129 in mice elevated the risk for CJD infection (as it does for sporadic and iatrogenic CJD in humans).
Transgenic mice (mPrP M129) injected with BSE appeared to produce mouse PrP^Sc, i.e. contracted BSE. Mice producing only hPrP V129 when injected with BSE remained symptom free at the conclusion of the study, 60 days longer than the time required for the appearance of CJD in mice of this genotype . Thus the hPrP V129 was probably unable to interact with bovine PrP^Sc M129 and thus transmit the disease but the mPrP M129 was able to interact with BSE PrP^Sc's.