Genetic control of scrapie and Creutzfeldt-Jakob disease in mice.
Genetic control of scrapie and Creutzfeldt-Jakob disease in mice.
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DOI：
10.4049/jimmunol.131.1.491
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发表时间：
1983-07
影响因子：
4.4
通讯作者：
D. Kingsbury;K. C. Kasper;D. Stites;J. Watson;R. Hogan;S. Prusiner
中科院分区：
文献类型：
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作者：
D. Kingsbury;K. C. Kasper;D. Stites;J. Watson;R. Hogan;S. Prusiner
通过测定小鼠脑内接种疫苗至出现神经功能障碍的时间，研究了近交系小鼠实验性痒病和克雅氏病（CJD）的遗传控制。每一株小鼠都易受感染；然而，瘙痒病和克雅氏病的潜伏期范围很广。最终发展为自身免疫性疾病的新西兰（NZ）小鼠，在脑内接种了10(6)ID50单位的钱德勒分离物中的痒病剂。NZW小鼠潜伏期小于95天；这是所有患有痒病的小鼠宿主所记录的最短时间。在NZB和NZB X W F1小鼠中，潜伏期约为130天，与BALB/c和C57BL小鼠相似。雄性和雌性NZ小鼠的瘙痒病潜伏期相同。当B10。将10(4)ID50单位的克雅氏病剂接种于Q和C57BL/6J小鼠脑内。隔离。这些观察结果确定了一个或多个基因座控制痒病和克雅氏病潜伏期的长度；编码较长潜伏期的等位基因似乎是常染色体显性的。当研究具有C57BL/10J背景的仅在H-2单倍型上不同的同源小鼠时，结果表明H-2复合体的D亚区在控制克雅氏病潜伏期的长度方面起着核心作用。D亚区q等位基因的潜伏期较短，而D等位基因的潜伏期较长。p、s、b和k等位基因的孵育时间为中等。我们建议用符号id -1来指定这个位于小鼠17号染色体上主要组织相容性（H-2）复合体D亚区的遗传位点。此外，对基因小鼠的观察为性别对克雅氏病潜伏期的影响提供了证据。在一些近亲繁殖的小鼠中，雄性小鼠的潜伏期明显短于雌性小鼠的潜伏期。这些对近交小鼠的研究确定了以前未被认识到的控制痒病和CJD潜伏期长度的基因。
Genetic control of experimental scrapie and Creutzfeldt-Jakob disease (CJD) was studied in inbred strains of mice by measuring the times from intracerebral inoculation with the agents to the onset of neurological dysfunction. Every strain of mice examined was susceptible to infection; however, a wide range of incubation times was found for both scrapie and CJD. New Zealand (NZ) mice, which eventually develop an autoimmune disorder, were inoculated intracerebrally with 10(6) ID50 units of the scrapie agent in a Chandler isolate. NZW mice showed incubation periods of less than 95 days; this is the shortest period recorded for any murine host with scrapie. In NZB and NZB X W F1 mice, the incubation periods were approximately 130 days and were similar to those in BALB/c and C57BL mice. Male and female NZ mice exhibited scrapie incubation periods of the same length. Similar results were obtained when B10.Q and C57BL/6J mice were inoculated intracerebrally with 10(4) ID50 units of the CJD agent in a K.Fu. isolate. These observations define a genetic locus or loci controlling the length of scrapie and CJD incubation periods; alleles coding for longer incubation times appear to be autosomal dominant. When congenic mice with a C57BL/10J background differing only in their H-2 haplotypes were studied, the results showed that the D subregion of the H-2 complex played a central role in controlling the length of the CJD incubation period. The q allele at the D subregion resulted in shorter incubation times, whereas the d allele resulted in long incubation times. The p, s, b, and k alleles gave intermediate incubation times. We propose the symbol PID-1 for designating this genetic locus which is located within the D subregion of the major histocompatibility (H-2) complex on murine chromosome 17. In addition, observations on congenic mice provide evidence for the influence of sex on CJD incubation periods. In some strains of inbred mice, males showed significantly shorter incubation periods compared with those for females with experimental CJD. These studies with inbred mice have defined previously unrecognized genes that control the length of scrapie and CJD incubation periods.