Cited by 3,073Genetic Neurodegenerative DiseasesGenetics and Neurodevelopmental DisordersAmyotrophic Lateral Sclerosis Research

Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice

Open access
Mangiarini, Laura, Sathasivam, Kirupa, Seller, Mary, Cozens, Barbara, Harper, Alex, Hetherington, Colin, Lawton, Martin, Trottier, Yvon +3 more·1996·Cell

Abstract

Huntington's disease (HD) is one of an increasing number of neurodegenerative disorders caused by a CAG/polyglutamine repeat expansion. Mice have been generated that are transgenic for the 5' end of the human HD gene carrying (CAG)115-(CAG)150 repeat expansions. In three lines, the transgene is ubiquitously expressed at both mRNA and protein level. Transgenic mice exhibit a progressive neurological phenotype that exhibits many of the features of HD, including choreiform-like movements, involuntary stereotypic movements, tremor, and epileptic seizures, as well as nonmovement disorder components. This transgenic model will greatly assist in an eventual understanding of the molecular pathology of HD and may open the way to the testing of intervention strategies.

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Crossref · 10.1016/s0092-8674(00)81369-0

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Authors
Mangiarini, L., Sathasivam, K., Seller, M., Cozens, B., Harper, A., Hetherington, C., Lawton, M., Trottier, Y., Lehrach, H., Davies, S. W., & Bates, G. P.
Affiliations
  • Guy's Hospital (GB)
  • University College London (GB)
  • St Thomas' Hospital (GB)
  • John Radcliffe Hospital (GB)
  • Centre National de la Recherche Scientifique (FR)
  • Max Planck Institute for Molecular Genetics (DE)
Corresponding author
Bates, Gillian P
Venue
Cell
Publisher
Elsevier BV
Published
1996-11
Volume
87
Issue
3
Pages
493-506
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2062682951
Cited by
3,073
References
31
Citations by year
2026: 52 · 2025: 59 · 2024: 76 · 2023: 77 · 2022: 92 · 2021: 124 · 2020: 92 · 2019: 108 · 2018: 132 · 2017: 109 · 2016: 112 · 2015: 121 · 2014: 144 · 2013: 124 · 2012: 149
FWCI
27.67
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
Huntington's disease, CAG repeat expansion, polyglutamine, exon 1, transgenic mice, neurodegeneration, choreiform movements, stereotyped movements, tremor, epileptic seizures, animal models
MeSH terms
Huntingtin Protein, Animals, Brain, Disease Models, Animal, Exons, Female, Humans, Huntington Disease, Male, Mice, Neurologic Mutants, Mice, Transgenic, Nerve Tissue Proteins, Nuclear Proteins, Phenotype, Spinal Cord, Trinucleotide Repeats, Transgenes, Mice

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