Kim Y S, Carp R I, Callahan S M, Natelli M, Wisniewski H M
New York State Office of Mental Retardation and Developmental Disabilities, Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
J Neuropathol Exp Neurol. 1990 Mar;49(2):106-13. doi: 10.1097/00005072-199003000-00003.
In previous studies we showed that C57BL mice injected stereotactically in the cerebellum with the 22L scrapie strain had a significantly shorter incubation period than those injected with the same agent in other brain regions. In mice injected in the cerebellum, vacuolization was limited to the cerebellum, medulla and mesencephalon, whereas injection into forebrain regions resulted in vacuolization in all brain regions. The studies suggested that the cerebellum had a selective vulnerability for 22L. In this study we examined the interaction between host genotype and selective vulnerability of specific brain regions. The mouse gene that has the most profound effect on pathogenesis, particularly incubation period, is termed Sinc (scrapie incubation). Groups of mice with three genotypes of Sinc (s7s7, p7p7 and their F1 cross, s7p7) were injected with 22L into the cerebral cortex, thalamus or cerebellum. Analysis of incubation periods showed that, regardless of the host genotype, the cerebellum injection group had a significantly shorter incubation period than groups injected in other regions. After cerebellum injection vacuolization was limited to the cerebellum, medulla and mesencephalon in all three host genotypes. The location of vacuoles within the cerebellum differed depending upon the host strain. Vacuolization developed almost exclusively in grey matter in s7s7 mice, mainly in white matter in p7p7 mice, and in both grey and white matter in F1 mice. These results demonstrate that the selective vulnerability of the cerebellum to induction of clinical disease by 22L does not depend on host genotype, but host genotype does affect lesion distribution within the cerebellum.
在先前的研究中，我们发现，经立体定位向C57BL小鼠的小脑注射22L瘙痒病毒株后，其潜伏期明显短于向其他脑区注射相同毒株的小鼠。在向小脑注射的小鼠中，空泡化仅限于小脑、延髓和中脑，而向前脑区域注射则导致所有脑区出现空泡化。这些研究表明，小脑对22L具有选择性易损性。在本研究中，我们检测了宿主基因型与特定脑区选择性易损性之间的相互作用。对发病机制，尤其是潜伏期影响最为深远的小鼠基因被称为Sinc（瘙痒病潜伏期）。将具有三种Sinc基因型（s7s7、p7p7及其F1杂交种s7p7）的小鼠组分别向大脑皮层、丘脑或小脑注射22L。潜伏期分析表明，无论宿主基因型如何，小脑注射组的潜伏期均明显短于其他区域注射组。小脑注射后，所有三种宿主基因型的空泡化均仅限于小脑、延髓和中脑。小脑内空泡的位置因宿主品系而异。在s7s7小鼠中，空泡化几乎仅发生在灰质中；在p7p7小鼠中，主要发生在白质中；而在F1小鼠中，灰质和白质中均有发生。这些结果表明，小脑对22L诱导临床疾病的选择性易损性不依赖于宿主基因型，但宿主基因型确实会影响小脑内病变的分布。
