Hoffman P M, Rohwer R G, MacAuley C, Bilello J A, Hartley J W, Morse H C
Proc Natl Acad Sci U S A. 1987 Jun;84(11):3866-70. doi: 10.1073/pnas.84.11.3866.
It has been shown that the autosomal recessive mutation, gray tremor (gt) was associated in the homozygous state (gt/gt) with a rapidly fatal spongiform encephalopathy. Heterozygotes (+/gt) developed mild asymptomatic spongiform brain lesions as did recipient inbred mice inoculated with gt/gt brain homogenates, some of whom also showed behavioral abnormalities [Sidman, R. L., Kinney, H. C. & Sweet, H. O. (1985) Proc. Natl. Acad. Sci. USA 82, 253-257]. In these studies, inbred NFS/N mice inoculated intracerebrally at birth or as adults with gt/gt or first passage gt brain homogenates developed a progressive disease characterized by tremor, ataxia, and spasticity. The symptoms were milder and more slowly progressive than in the gt/gt homozygote, in the paralytic syndrome that followed neonatal inoculation of NFS/N mice with a wild murine leukemia virus (Cas-Br-M MuLV), or in the rapidly progressive ataxia and terminal bradykinesia that followed scrapie inoculation of NFS/N mice. The noninflammatory spongiform encephalopathy in affected NFS/N mice resembled that observed in gt/gt homozygotes, +/gt heterozygotes, and asymptomatic recipient inbred mice inoculated with gt/gt brain homogenates. Neither infectious MuLV nor MuLV proteins were detected in gt/gt brain homogenates or in affected recipient mouse brains. Scrapie-associated fibrils, readily identifiable in subcellular fractions of brains from scrapie-inoculated NFS/N mice, were not detected in similar brain fractions from NFS/N mice inoculated with gt brain homogenates. These results confirm and extend the suggestion that gt spongiform encephalopathy has both heritable and transmissible properties. Moreover, the transmissible agent of gt disease differs from both Cas-Br-M MuLV and scrapie in its disease-inducing properties in NFS/N mice. The capacity of NFS/N mice to express transmitted gt encephalopathy as clinical disease, to rapidly express Cas-Br-M MuLV spongiform encephalomyelopathy, and to develop mouse-adapted scrapie after a very short incubation time suggest a distinct sensitivity of NFS/N mice to transmissible spongiform encephalopathy.
研究表明，常染色体隐性突变——灰色震颤（gt）在纯合状态（gt/gt）下与一种快速致死性海绵状脑病相关。杂合子（+/gt）会出现轻度无症状性海绵状脑损伤，接种gt/gt脑匀浆的受体近交系小鼠也是如此，其中一些小鼠还表现出行为异常[西德曼，R. L.，金尼，H. C. & 斯威特，H. O.（1985年）《美国国家科学院院刊》82，253 - 257]。在这些研究中，出生时或成年后经脑内接种gt/gt或初代传代gt脑匀浆的近交系NFS/N小鼠会患上一种进行性疾病，其特征为震颤、共济失调和痉挛。与gt/gt纯合子、新生期接种野生型鼠白血病病毒（Cas - Br - M MuLV）后的NFS/N小鼠出现的麻痹综合征，或接种羊瘙痒病后的NFS/N小鼠快速进展的共济失调和终末期运动徐缓相比，这些症状更轻且进展更慢。受影响的NFS/N小鼠中的非炎性海绵状脑病与在gt/gt纯合子、+/gt杂合子以及接种gt/gt脑匀浆的无症状受体近交系小鼠中观察到的相似。在gt/gt脑匀浆或受影响的受体小鼠脑中均未检测到传染性MuLV或MuLV蛋白。在接种羊瘙痒病的NFS/N小鼠脑的亚细胞组分中易于识别的羊瘙痒病相关纤维，在接种gt脑匀浆的NFS/N小鼠的类似脑组分中未检测到。这些结果证实并扩展了关于gt海绵状脑病具有遗传性和传染性的观点。此外，gt病的传染因子在NFS/N小鼠中的致病特性与Cas - Br - M MuLV和羊瘙痒病均不同。NFS/N小鼠将传播的gt脑病表现为临床疾病、快速表现出Cas - Br - M MuLV海绵状脑脊髓病以及在非常短的潜伏期后发展为小鼠适应性羊瘙痒病的能力，表明NFS/N小鼠对传染性海绵状脑病具有独特的敏感性。
