M83转基因小鼠突触核蛋白的“ Prion样”繁殖取决于小鼠的基因型和接种物类型。,Journal of Neurochemistry

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M83转基因小鼠突触核蛋白的“ Prion样”繁殖取决于小鼠的基因型和接种物类型。
Journal of Neurochemistry ( IF 4.2 ) Pub Date : 2017-08-05 , DOI: 10.1111/jnc.14139
Dorian Sargent ₁ , Jérémy Verchère ₁ , Corinne Lazizzera ₁ , Damien Gaillard ₁ , Latifa Lakhdar ₁ , Nathalie Streichenberger ₂ , Eric Morignat ₁ , Dominique Bétemps ₁ , Thierry Baron ₁

Affiliation

M83转基因小鼠是人类突触核蛋白病的模型，其发展为与脑和脊髓中病理性Ser129磷酸化α-突触核蛋白（α-synP）积累相关的严重运动障碍。脑内接种患病M83小鼠的脑提取物可以加速M83疾病。最近也已经使用外围途径描述了这一点，将重组的预先形成的α-syn原纤维注入肌肉或腹膜。在这里，我们通过腹膜内和/或脑内途径为纯合和/或半合M83新生儿接种了两种不同的脑提取物：一种是从患病的M83小鼠中接种了其他有病的M83小鼠的脑中提取物，另一种是从人多系统萎缩中获得的来源在M83小鼠中传代。使用ELISA和Western blot检测α-synP证实了这种疾病的发生。α-synP在中枢神经系统中的分布是相似的，与接种物或接种途径无关，这与先前描述M83疾病的研究一致。ELISA测试显示，至少在接种IC后，纯合子中的α-synP水平高于半合子的M83小鼠。有趣的是，在前两代，用多系统萎缩接种物接种的M83小鼠的ELISA检测到的α-synP的免疫反应性显着低于接种M83接种物的M83小鼠。脑内和腹膜内接种患病小鼠的脑提取物，可加速突触核蛋白病直至临床疾病的“类on病毒”传播。但是，这种加速

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'Prion-like' propagation of the synucleinopathy of M83 transgenic mice depends on the mouse genotype and type of inoculum.

The M83 transgenic mouse is a model of human synucleinopathies that develops severe motor impairment correlated with accumulation of the pathological Ser129-phosphorylated α-synuclein (α-synP ) in the brain and spinal cord. M83 disease can be accelerated by intracerebral inoculation of brain extracts from sick M83 mice. This has also recently been described using peripheral routes, injecting recombinant preformed α-syn fibrils into the muscle or the peritoneum. Here, we inoculated homozygous and/or hemizygous M83 neonates via the intraperitoneal and/or intracerebral routes with two different brain extracts: one from sick M83 mice inoculated with brain extract from other sick M83 mice, and the other derived from a human multiple system atrophy source passaged in M83 mice. Detection of α-synP using ELISA and western blot confirmed the disease in mice. The distribution of α-synP in the central nervous system was similar, independently of the inoculum or inoculation route, consistent with previous studies describing M83 disease. ELISA tests revealed higher levels of α-synP in homozygous than in hemizygous sick M83 mice, at least after IC inoculation. Interestingly, the immunoreactivity of α-synP detected by ELISA was significantly lower in M83 mice inoculated with the multiple system atrophy inoculum than in M83 mice inoculated with the M83 inoculum, at the first two passages. 'Prion-like' propagation of the synucleinopathy up to the clinical disease was accelerated by both intracerebral and intraperitoneal inoculations of brain extracts from sick mice. This acceleration, however, depends on the levels of α-syn expression by the mouse and the type of inoculum.

更新日期：2019-11-01

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