Non-prion-type transmission in A53T α-synuclein transgenic mice: a normal component of spinal homogenates from naïve non-transgenic mice induces robust α-synuclein pathology
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The injection of tissue homogenates from diseased animals into naïve animals to induce a neurodegenerative phenotype is a feature that defines “prion-like” transmission. Several recent studies have demonstrated that transgenic mice expressing human A53T-α-synuclein (αS; Line M83), respond to injections of CNS tissue homogenates containing abundant αS pathology by accelerated onset of CNS pathology with concurrent accelerated motor impairment [1, 3, 4, 5, 9]. Homozygous line M83+/+ A53T αS mice naturally develop a severe motor phenotype between 8 and 16 months that is associated with the formation of αS inclusions in the spinal cord, brain stem, thalamus, periaqueductal gray, and motor cortex . Hemizygous M83+/− mice do not begin to develop these phenotypes until 21 months or later , but disease can be induced earlier by injection of CNS homogenates from affected M83+/+ mice [5, 9]. Although purified αS protein fibrils can reproduce the effects seen with tissue homogenates [1, 3, 6...
KeywordsMotor Phenotype Intrahippocampal Injection Spinal Cord Homogenate Asymptomatic Mouse Accelerate Disease Onset
This study was supported by NINDS R01-NS089622 (BG) and R01-NS092788 (DB).
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Conflict of interest
The author(s) declare that they have no other competing interests.
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