Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse

Jared M. Ordway, Sara Tallaksen-Greene, Claire Anne Gutekunst, Eve M. Bernstein, Jamie A. Cearley, Howard W. Wiener, Leon S. Dure IV, Russell Lindsey, Steven M. Hersch, Richard S Jope, Roger L. Albin, Peter J. Detloff

Research output: Contribution to journalArticle

301 Citations (Scopus)

Abstract

The mutations responsible for several human neurodegenerative disorders are expansions of translated CAG repeats beyond a normal size range. To address the role of repeat context, we have introduced a 146 unit CAG repeat into the mouse hypoxanthine phosphoribosyltransferase gene (Hprt). Mutant mice express a form of the HPRT protein that contains a long polyglutamine repeat. These mice develop a phenotype similar to the human translated CAG repeat disorders. Repeat containing mice show a late onset neurological phenotype that progresses to premature death. Neuronal intranuclear inclusions are present in affected mice. Our results show that CAG repeats do not need to be located within one of the classic repeat disorder genes to have a neurotoxic effect.

Original languageEnglish
Pages (from-to)753-763
Number of pages11
JournalCell
Volume91
Issue number6
DOIs
StatePublished - Dec 12 1997
Externally publishedYes

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Hypoxanthine Phosphoribosyltransferase
Intranuclear Inclusion Bodies
Genes
Phenotype
Premature Mortality
Proteins
Neurodegenerative Diseases
Reference Values
Mutation
polyglutamine

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Ordway, J. M., Tallaksen-Greene, S., Gutekunst, C. A., Bernstein, E. M., Cearley, J. A., Wiener, H. W., ... Detloff, P. J. (1997). Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse. Cell, 91(6), 753-763. https://doi.org/10.1016/S0092-8674(00)80464-X

Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse. / Ordway, Jared M.; Tallaksen-Greene, Sara; Gutekunst, Claire Anne; Bernstein, Eve M.; Cearley, Jamie A.; Wiener, Howard W.; Dure IV, Leon S.; Lindsey, Russell; Hersch, Steven M.; Jope, Richard S; Albin, Roger L.; Detloff, Peter J.

In: Cell, Vol. 91, No. 6, 12.12.1997, p. 753-763.

Research output: Contribution to journalArticle

Ordway, JM, Tallaksen-Greene, S, Gutekunst, CA, Bernstein, EM, Cearley, JA, Wiener, HW, Dure IV, LS, Lindsey, R, Hersch, SM, Jope, RS, Albin, RL & Detloff, PJ 1997, 'Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse', Cell, vol. 91, no. 6, pp. 753-763. https://doi.org/10.1016/S0092-8674(00)80464-X
Ordway JM, Tallaksen-Greene S, Gutekunst CA, Bernstein EM, Cearley JA, Wiener HW et al. Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse. Cell. 1997 Dec 12;91(6):753-763. https://doi.org/10.1016/S0092-8674(00)80464-X
Ordway, Jared M. ; Tallaksen-Greene, Sara ; Gutekunst, Claire Anne ; Bernstein, Eve M. ; Cearley, Jamie A. ; Wiener, Howard W. ; Dure IV, Leon S. ; Lindsey, Russell ; Hersch, Steven M. ; Jope, Richard S ; Albin, Roger L. ; Detloff, Peter J. / Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse. In: Cell. 1997 ; Vol. 91, No. 6. pp. 753-763.
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