The invention provides a non-human animal model of Parkinson's disease based on animals which carry a modified version of the GDNF gene which comprises recombinase target sites flanking an essential part of said gene and a transgene which encodes for a recombinase specific for the target sites in the GDNF gene and which can be activated at will by administering a given compound to the animal. Activation of the recombinase in adult animals leads to a progressive catecholaminergic neuronal death. The invention also provides the use of said animals for the study of the pathogenesis of Parkinson's disease and for the identification of GDNF targets (which preserve the neurons from degeneration) as well as GDNF agonists and activators.
本发明提供了一种帕
金森病的非人类动物模型,该模型基于携带改良版 GDNF
基因的动物,该改良版 GDNF
基因包括
重组酶靶位点和转
基因,前者位于所述
基因重要部分的侧翼,后者编码针对 GDNF
基因中靶位点的特异性
重组酶,可通过给动物施用特定化合物随意激活。成年动物体内
重组酶的激活会导致
儿茶酚胺能神经元逐渐死亡。本发明还提供了将上述动物用于研究帕
金森病的发病机理、鉴定 GDNF 靶点(使神经元免于退化)以及 GDNF 激动剂和激活剂的方法。