Mutation frequency is reduced in the cerebellum of Big Blue® mice overexpressing a human wild type SOD1 gene

Makoto Kunishige, Kathleen A. Hill, Amanda M. Riemer, Kelly D. Farwell, Asanga Halangoda, Ernst Heinmöller, Stephen Moore, Dianna M. Turner, Steve S. Sommer

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive paralytic disorder caused by motor neuron degeneration. A similar disease phenotype is observed in mice overexpressing a mutant human hSOD1 gene (G93A, 1Gurd1). Mice transgenic for lacI (Big Blue®) and human mutant (1Gurd1, Mut hSOD1) or wild type (2Gur, Wt hSOD1) SOD1 genes were used to examine spontaneous mutation, oxidative DNA damage, and neurodegeneration in vivo. The frequency and pattern of spontaneous mutation were determined for forebrain (90% glia), cerebellum (90% neurons) and thymus from 5-month-old male mice. Mutation frequency is not elevated significantly and mutation pattern is unaltered in Mut hSOD1 mice compared to control mice. Mutation frequency is reduced significantly in the cerebellum of Wt hSOD1 mice (1.6 × 10-5; P = 0.0093; Fisher's Exact Test) compared to mice without a human transgene (2.7 × 10-5). Mutation pattern is unaltered. This first report of an endogenous factor that can reduce in vivo, the frequency of spontaneous mutation suggests potential strategies for lowering mutagenesis related to aging, neurodegeneration, and carcinogenesis.

Original languageEnglish (US)
Pages (from-to)139-149
Number of pages11
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume473
Issue number2
DOIs
StatePublished - Feb 20 2001
Externally publishedYes

Fingerprint

Mutation Rate
Cerebellum
Genes
Mutation
Nerve Degeneration
Amyotrophic Lateral Sclerosis
Motor Neurons
Prosencephalon
Transgenes
Neuroglia
Mutagenesis
Thymus Gland
Transgenic Mice
DNA Damage
Carcinogenesis
Phenotype
Neurons

Keywords

  • Amyotrophic lateral sclerosis
  • LacI
  • Neurodegeneration
  • Oxidative damage
  • Superoxide dismutase

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

Cite this

Mutation frequency is reduced in the cerebellum of Big Blue® mice overexpressing a human wild type SOD1 gene. / Kunishige, Makoto; Hill, Kathleen A.; Riemer, Amanda M.; Farwell, Kelly D.; Halangoda, Asanga; Heinmöller, Ernst; Moore, Stephen; Turner, Dianna M.; Sommer, Steve S.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 473, No. 2, 20.02.2001, p. 139-149.

Research output: Contribution to journalArticle

Kunishige, Makoto ; Hill, Kathleen A. ; Riemer, Amanda M. ; Farwell, Kelly D. ; Halangoda, Asanga ; Heinmöller, Ernst ; Moore, Stephen ; Turner, Dianna M. ; Sommer, Steve S. / Mutation frequency is reduced in the cerebellum of Big Blue® mice overexpressing a human wild type SOD1 gene. In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 2001 ; Vol. 473, No. 2. pp. 139-149.
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