Two prion strains with identical incubation periods in mice exhibited
distinct incubation periods and different neuropathological profiles u
pon serial transmission to transgenic mice expressing chimeric Syrian
hamster/mouse (MH2M) prion protein (PrP) genes [Tg(MH2M) mice] and sub
sequent transmission to Syrian hamsters. After transmission to Syrian
hamsters, the Me7 strain was indistinguishable from the previously est
ablished Syrian hamster strain Sc237, despite having been derived from
an independent ancestral source, This apparent convergence suggests t
hat prion diversity may be limited. The Me7 mouse strain could also be
transmitted directly to Syrian hamsters, but when derived in this way
, its properties were distinct from those of Me7 passaged through Tg(M
H2M) mice. The Me7 strain did not appear permanently altered in either
case, since the original incubation period could be restored by effec
tively reversing the series of passages, Prion diversity enciphered in
the conformation of the scrapie isoform of PrP (PrPSc) (G. C. Telling
et al., Science 274:2079-2082, 1996) seems to be limited by the seque
nce of the PrP substrates serially converted into PrPSc, while prions
are propagated through interactions between the cellular and scrapie i
soforms of PrP.