Kingsbury D T, Kasper K C, Stites D P, Watson J D, Hogan R N, Prusiner S B
J Immunol. 1983 Jul;131(1):491-6.
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.
通过测量从脑内接种病原体到出现神经功能障碍的时间，对近交系小鼠的实验性瘙痒病和克雅氏病（CJD）的遗传控制进行了研究。所检查的每株小鼠都易受感染；然而，瘙痒病和CJD都发现了广泛的潜伏期。最终会发生自身免疫性疾病的新西兰（NZ）小鼠，脑内接种了10⁶ ID50单位的钱德勒分离株中的瘙痒病病原体。NZW小鼠的潜伏期不到95天；这是任何感染瘙痒病的鼠类宿主记录的最短时间。在NZB和NZB×W F1小鼠中，潜伏期约为130天，与BALB/c和C57BL小鼠的潜伏期相似。雄性和雌性NZ小鼠的瘙痒病潜伏期长度相同。当用10⁴ ID50单位的K.Fu.分离株中的CJD病原体脑内接种B10.Q和C57BL/6J小鼠时，也得到了类似的结果。这些观察结果确定了一个控制瘙痒病和CJD潜伏期长度的基因座或多个基因座；编码较长潜伏期的等位基因似乎是常染色体显性的。当研究仅在其H-2单倍型上不同的具有C57BL/10J背景的同源小鼠时，结果表明H-2复合体的D亚区在控制CJD潜伏期长度方面起核心作用。D亚区的q等位基因导致较短的潜伏期，而d等位基因导致较长的潜伏期。p、s、b和k等位基因产生中等潜伏期。我们建议用符号PID-1来命名这个位于小鼠17号染色体上主要组织相容性（H-2）复合体D亚区内的基因座。此外，对同源小鼠的观察为性别对CJD潜伏期的影响提供了证据。在一些近交系小鼠品系中，雄性小鼠的潜伏期明显短于患有实验性CJD的雌性小鼠。这些对近交系小鼠的研究确定了以前未被认识的控制瘙痒病和CJD潜伏期长度的基因。
