Emerging Animal Models for Research

Mutations in the LRRK2 and SNCA (alpha synuclein) genes are associated with familial Parkinson's disease. Each of these four rat models feature a transgene expressing one of these two human genes, either as wild type or with relevant mutations. Mutations in alpha-synuclein and LRRK2 cause familial PD (Park 1 and Park 8) in a dominant inheritance manner. For alpha synuclein, A53T, A30P, E46K mutations and gene duplication/triplication can lead to PD. For LRRK2, G2019S is the most prevalent mutation found in familial and sporadic PD. R1441G is another prominent mutation, which was identified during the process of genetic mapping and disease gene cloning. The rat as an experimental organism can offer some unique strengths compared to mice. For example, rats can perform more sophisticated behavioral tasks, and are better suited for electrophysiological multichannel recordings. The nigrostriatal circuit of the rat is also more sensitive to insults than that of mice. In these transgenic rats, transgenes are expressed to make full length proteins (please see Expression Analysis provided under Related Publications). These animals are being analyzed for their pathological, neurochemical, and behavioral phenotypes. Cannon et al., have shown Parkinsonian phenotype in the Human Alpha Synuclein E46K Rat (Model 10679).

Dopamine neurons are susceptible to damage/loss in Parkinson's disease and the hTH-GFP rat provides a research tool for studying this process. The hTH-GFP rat carries an EGFP transgene driven by the human Tyrosine Hydroxylase promoter. High-level specific EGFP expression is seen in dopaminergic neurons. The hTH-GFP rat is useful for in vivo and in vitro studies of dopamine neuron function and degeneration in Parkinson's disease.

^** Note: Distribution of the Human LRRK2 R1441G Rat (Model 10677) has been discontinued. Expression analysis shows that the transgene expresses poorly.