Neurodegeneration in Lurcher mice caused by mutation in δ2 glutamate receptor gene

Jian Zuo, Philip L. De Jager, Kanji A. Takahashi, Weining Jiang, David J. Linden, Nathaniel Heintz

Research output: Contribution to journalArticlepeer-review

458 Scopus citations


Lurcher (Lc) is a spontaneous, semidominant mouse neurological mutation. Heterozygous Lurcher mice (Lc/+)display ataxia as a result of a selective, cell-autonomous and apoptotic death of cerebellar Purkinje cells during postnatal development. Homozygous Lurcher mice (Lc/Lc) die shortly after birth because of a massive loss of mid- and hindbrain neurons during late embryogenesis. We have used positional cloning to identify the mutations responsible for neurodegeneration in two independent Lc alleles as G-to-A transitions that change a highly, conserved alanine to a threonine residue in transmembrane domain III of the mouse δ2 glutamate receptor gene (GluRδ2). Lc/+ Purkinje cells have a very high membrane conductance and a depolarized resting potential, indicating the presence of a large, constitutive inward current. Expression of the mutant GluRδ2(Lc) protein in Xenopus oocytes confirmed these results, demonstrating that Lc is inherited as a neurodegenerative disorder resulting from a gain-of-function mutation in a glutamate receptor gene. Thus the activation of apoptotic neuronal death in Lurcher mice may provide a physiologically relevant model for excitotoxic cell death.

Original languageEnglish (US)
Pages (from-to)769-773
Number of pages5
Issue number6644
StatePublished - 1997

ASJC Scopus subject areas

  • General


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