title: The human homologue of the weaver mouse gene in familial and sporadic Parkinson's disease.
abstract: The pathological hallmark of Parkinson's disease is cell death of dopaminergic neurons in the substantia nigra, resulting in striatal dopaminergic deficit and a clinical syndrome dominated by disorders of movement. The cause for this cell loss is unknown, but the possibility of a contributing genetic factor is increasingly recognized. Homozygous weaver mice, a mutant mouse strain, display progressive postnatal depletion of dopaminergic cells in the mesencephalon and have thus been proposed as an animal model for Parkinson's disease. Recently, mGIRK2, a putative G-protein inward rectifier K+ channel, has been identified as the causative gene in the weaver mouse and a homozygous mutation has been described in the H5 pore region of this channel. The human homologue of mGIRK2, KCNJ7 or hiGIRK2, has previously been isolated on chromosome 21q22.1. A possible involvement of this gene in the pathogenesis of Parkinson's disease has been discussed. To evaluate the possibility of a shared genetic defect in weaver mouse and Parkinson's disease, we analysed the H5 pore region of hiGIRK2 in familial and sporadic cases of Parkinson's disease. The sequence was normal in all cases examined, suggesting a differing aetiology of nigral cell loss in Parkinson's disease and weaver mice.
authors: University Department of Clinical Neurology (Neurogenetics and Movement Disorders Section), Institute of Neurology, London, U.K.
authors: O
authors: O
authors: Bandmann
authors: M B
authors: MB
authors: Davis
authors: C D
authors: CD
authors: Marsden
authors: N W
authors: NW
authors: Wood
mesh_terms: D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D006801:Humans; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000235:genetics*; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000235:genetics*; D018272:Porins / Q000235:genetics; D015221:Potassium Channels / Q000235:genetics* / Q000648:ultrastructure; D024661:Potassium Channels, Inwardly Rectifying; D012689:Sequence Homology, Nucleic Acid
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018272:Porins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D004247:DNA