C10840: Conditional Alpha Synuclein Transgenic Mice
Value Proposition:
JHU Inventors have developed conditional alpha-synuclein transgenic mice that can express A53T, E46K or C-terminally truncated alpha-synuclein.
ADVANTAGES - Effects of different pathological variants of the alpha-synuclein protein can be directly compared in the ROSA26-alphaSyn mice since variants are expressed at equivalent levels from the same stable promoter at identical copy number in the same neurons. - Two pathological alpha-synuclein variants from opposite alleles can be co-expressed in ROSA26-alphaSyn mice at equivalent levels in the same neurons to determine how their interactions precipitate to pathology or compromise neuronal viability. - ROSA26-alphaSyn mice are ideally suited for investigating potential gene-environment interactions with dopamine neuron-specific toxins, and any differential interaction of dopaminergic toxins with various pathogenic alpha-synuclein variants can be directly compared.
Technical Details:
Parkinson's disease (PD) is the most common progressive neurodegenerative movement disorder. A hallmark of PD is appearance of neuronal cell inclusions called Lewy bodies. alpha-Synuclein protein is a major component of Lewy bodies. Alpha-synuclein plays an important role in the pathogenesis of familial and sporadic PD. For example, mutations of the alpha-synuclein gene are thought to cause autosomal dominant familial Parkinson’s disease. To model alpha-synuclein-linked disease in vivo, JHU scientists have developed transgenic mouse models that express wild-type or mutant human alpha-synuclein from a variety of neuronal-selective heterologous promoter elements. These mice exhibit a variety of behavioral and neuropathological features resembling some aspects of Parkinson’s disease, but appear to lack robust or progressive nigrostriatal dopaminergic neuronal degeneration.
Looking for Partners:
The ROSA26-alpha Syn mice offer an important resource for modeling various aspects of PD. These mice allow the expression of disease-associated alpha-synuclein variants selectively in nigrostriatal pathway dopaminergic neurons in order to evaluate their potentially pathogenic affects with age. Transgene expression in these mice is driven by the well-characterized neuronal-specific, endogenous murine ROSA26 promoter in a Cre-dependent manner.This system permits the expression of alpha -synuclein variants in virtually any neuronal population in the brain depending upon the availability of suitable Cre driver lines.
