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

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

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Ordway, J. M., Tallaksen-Greene, S., Gutekunst, C. A., Bernstein, E. M., Cearley, J. A., Wiener, H. W., Dure IV, L. S., Lindsey, R., Hersch, S. M., Jope, R. S., Albin, R. L., & 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