Cited by 555Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersGenetic Neurodegenerative Diseases

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

Zuo, Jian, De Jager, Philip L., Takahashi, Kanji A., Jiang, Weining, Linden, David J., Heintz, Nathaniel·1997·Nature

Abstract

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 delta2 glutamate receptor gene (GluR delta2). 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 GluR delta2(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.

Integrity signals

Registry

Crossref · 10.1038/42009

Cites

22 of 22 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Heterozygous Lurcher mice lose all cerebellar Purkinje cells because of a gain-of-function mutation in the δ2 glutamate receptor gene.

    “Heterozygous Lurcher mice lose 100% of their cerebellar Purkinje cells due to a gain-of-function mutation in the δ2 glutamate receptor gene [283],”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Zuo, J., De Jager, P. L., Takahashi, K. A., Jiang, W., Linden, D. J., & Heintz, N.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Johns Hopkins University (US)
Corresponding author
Heintz, Nathaniel
Venue
Nature
Published
1997-08-21
Volume
388
Issue
6644
Pages
769-773
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W1523646668
Cited by
554
References
22
Citations by year
2026: 5 · 2025: 8 · 2024: 6 · 2023: 12 · 2022: 9 · 2021: 17 · 2020: 18 · 2019: 8 · 2018: 9 · 2017: 9 · 2016: 14 · 2015: 15 · 2014: 20 · 2013: 17 · 2012: 23
FWCI
12.06
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • American-Scandinavian Foundation
  • McKnight Foundation
  • National Fish and Wildlife Foundation
  • National Alliance for Research on Schizophrenia and Depression
  • National Institutes of Health
  • Comisión de Investigaciones Científicas
  • National Institute of Mental Health (MH 51106)
  • National Institute of General Medical Sciences
  • National Marine Fisheries Service
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Keywords
neurodegeneration, Purkinje cell death, apoptosis, gain-of-function mutations, excitotoxic cell death, cerebellum, ataxia, positional cloning
MeSH terms
Amino Acid Sequence, Animals, Chromosome Mapping, Electrophysiology, Exons, Introns, Mice, Inbred Strains, Mice, Neurologic Mutants, Molecular Sequence Data, Nerve Degeneration, Nervous System Diseases, Purkinje Cells, Recombinant Proteins, Xenopus laevis, Point Mutation, Sequence Homology, Amino Acid, Receptors, Glutamate, Polymorphism, Single-Stranded Conformational, Mice, In Vitro Techniques

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review