Scrapie strains

BSE is not transmissible to humans. However, there appears to be a strong connection between BSE and a variation of Creutzfeldt-Jakob disease, known as variant Creutzfeldt-Jakob disease (vCJD), another disease grouped with other TSEs. Evidence to date indicates that there has never been a case of vCJD transmission from person to person, but rather it is thought to spread from the consumption of cattle products contaminated with BSE. BSE and vCJD share many characteristics, to the point of being nearly indistinguishable from each other. Clinical studies have shown that mice inoculated with BSE showed the same pattern of incubation time, clinical signs, and brain lesions as mice inoculated with tissues from patients with vCJD. This provides evidence that BSE and vCJD are of the same strain . Furthermore, these two diseases were not similar to other TSEs such as sporadic CJD and known scrapies strains. 

As mentioned previously, assessment of scrapie strain diversity initially relied on transmission of natural isolates to inbred mice [33]. From such an approach, estimates of up to 20 strains were described [34, 35]. However, more recently, this estimate has been revised to three distinct strains, namely ME7 and 87A in short incubation time Prnp-a mice and 87V in long incubation time Prnp-b mice [4, 33, 36]. 

Bruce ME (1993) Scrapie strain variation and mutation. Br Med Bull 49 822-838... 

Fig. 4. PrP-res isolated from hamsters infected with different scrapie strains can determine the final conformation of the protease-resistant product. Radiolabeled hamster PrP-sen without the GPI anchor was mixed with hamster PrP-res isolated from the brains of hamsters infected with either hyper (Hy) or drowsy (Dy) scrapie in a cell-free conversion assay (Kocisko et al, 1994). The PrP-res was either pre-treated (+) or not (-) with proteinase K to remove any contaminating proteins (Bessen et al, 1995). The left side panel shows the radiolabeled PrP-sen in the reaction after a 2-day incubation and before digestion with proteinase K (-PK) and represents 10% of the total reaction. The right side panel shows the radiolabeled, protease-resistant product remaining after digestion of the reaction with proteinase K (+PK) and represents the remaining 90% of the reaction. Note the characteristic size shift of 1 to 2 kDa which is used to distinguish PrP-res from the hyper and drowsy scrapie strains (Bessen and Marsh, 1992a). There is no significant difference in the amount of protease-resistant product formed when PK pretreated or untreated PrP-res is used (53% vs. 48% for hyper PrP-res and 47% vs. 40% for drowsy PrP-res). Molecular mass markers are shown in kilodaltons on the right.

Kascsak and colleagues first observed that PrP-res associated with various murine scrapie strains differ in the relative proportions of PrP-res glycoforms (i.e., PrP molecules with 0, 1 or 2 N-linked glycans) (Kascsak... 

Effective in a lot of scrapie strains, rapid metabolism and excretion, toxic... 

Drug Tested on Scrapie Strain Success in Animal Treatment Suggested Mode of Action References... 

Garp, R.I., Ye, X., and Rubenstein, R. (1994). The nature of he scrapie agent. Biological characteristics of scrapie in different scrapie strain-host combinations. Ann. N.Y. Acad. Sd. 724, 221-234. 

Scrapie is a neurodegenerative disease with a long incubation period, known to occur in sheep and goats, however, mice and other small rodents can be infected with it (Hunter, 1972). Certain scrapie strains induce obesity in... 

Mice infected with certain strains of scrapie determine a significant increase in body weight in the preclinical phase of the disease (Carp et al., 1984). Regardless of the mouse strain, the scrapie strain ME7 injected in the hypothalamus-induced obesity (Carp et al., 1984, 1998 Kim et al., 1987, 1988). This effect was also observed for 22L scrapie strain injected in certain type of mice (Carp et al., 1984, 1998 Kim et al., 1987), but not for 139A (Carp et al., 1984, 1998 Kim et al., 1987, 1988) or 22A scrapie strains (Carp et al., 1984). 

L strain of scrapie injected in the cortex or hypothalamus of SJL mice induced obesity (Carter and Smith, 1984 Kim et al., 1987). However when injected in SAMP8, SAMRl, AKR (Carp et al., 1998), and CBA mice (Carp et al., 1984), the scrapie strain did not produce any differences in body weight. SJL-infected mice showed 73% and 70% increase in body weights when injected in hypothalamus or cortex, respectively, versus 36% increase in the control group. Furthermore, the weight difference became significant earlier, compared to when inoculated with 22L (10 weeks vs 12 weeks postinjection) (Kim et al., 1987). 

Carp, R.I., Meeker, H., Sersen, E., and Kozlowski, P. 1998. Analysis of the incubation periods, induction of obesity and histopathological changes in senescence-prone and senescence-resistant mice infected with various scrapie strains. J. Gen. Virol 79(Pt. 11), 2863-2869. 

All animal experiments were carried out in accordance with European, German, and USA legal and ethical regulations. Twenty outbred Syrian hamsters at an age of approximately 8 weeks were treated with 1-3 xlO 50% intracerebral lethal doses of scrapie strain 263K as described elsewhere. Twelve mock-infected hamsters of the same age were similarly treated with normal brain homogenate and served as controls. Five infected and three control hamsters each were sacrificed by euthanasia with CO2 at four time points 100... 

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