The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Mismatch repair gene Msh2 modifies the timing of early disease in HdhQ111 striatum
Abstract
Somatic instability of expanded HD CAG repeats that encode the polyglutamine tract in mutant huntingtin has been implicated in the striatal selectivity of Huntington's disease (HD) pathology. Here in Hdh(Q111) mice, we have tested whether a genetic background deficient in Msh2, expected to eliminate the unstable behavior of the 109 CAG array inserted into the murine HD gene, would alter the timing or striatal specificity of a dominant disease phenotype that predicts late-onset neurodegeneration. Our analyses of Hdh(Q111/+):Msh2(+/+) and Hdh(Q111/+): Msh2(-/-) progeny revealed that, while inherited instability involved Msh2-dependent and -independent mechanisms, lack of Msh2 was sufficient to abrogate progressive HD CAG repeat expansion in striatum. The absence of Msh2 also eliminated striatal mutant huntingtin with somatically expanded glutamine tracts and caused an approximately 5 month delay in nuclear mutant protein accumulation, but did not alter the striatal specificity of this early phenotype. Thus, somatic HD CAG instability appears to be a consequence of a striatal-selective disease process that accelerates the timing of an early disease phenotype, via expansion of the glutamine tract in mutant huntingtin. Therefore Msh2, as a striking modifier of early disease onset in a precise genetic HD mouse model, provides a novel target for the development of pharmacological agents that aim to slow pathogenesis in man.
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Genome maintenance mechanisms for preventing cancer
Hoeijmakers, J. H. J. (2001) · Nature · doi:10.1038/35077232 · Cited by 3,939
Trinucleotide repeat length instability and age of onset in Huntington's disease
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Neuroprotective Effects of Creatine in a Transgenic Mouse Model of Huntington's Disease
Ferrante, R. J., Andreassen, O. A., Jenkins, B. G., Dedeoglu, A., Kuemmerle, S., Kubilus, J. K., Kaddurah-Daouk, R., Hersch, S. M., & Beal, M. F. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-12-04389.2000 · Cited by 522
Therapeutic Effects of Coenzyme Q10and Remacemide in Transgenic Mouse Models of Huntington's Disease
Ferrante, R. J., Andreassen, O. A., Dedeoglu, A., Ferrante, K. L., Jenkins, B. G., Hersch, S. M., & Beal, M. F. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-05-01592.2002 · Cited by 391
Andreassen, O. A., Dedeoglu, A., Ferrante, R. J., Jenkins, B. G., Ferrante, K. L., Thomas, M., Friedlich, A., Browne, S. E., Schilling, G., Borchelt, D. R., et al. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0406 · Cited by 293
Cited by
Bates, G. P., Dorsey, R., Gusella, J. F., Hayden, M. R., Kay, C., Leavitt, B. R., Nance, M., Ross, C. A., Scahill, R. I., Wetzel, R., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.5 · Cited by 1,641
DNA Mismatch Repair: Functions and Mechanisms
Iyer, R. R., Pluciennik, A., Burdett, V., & Modrich, P. L. (2006) · Chemical Reviews · doi:10.1021/cr0404794 · Cited by 905
Repeat instability: mechanisms of dynamic mutations
Pearson, C. E., Edamura, K. N., & Cleary, J. D. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1689 · Cited by 924
CAG Repeat Not Polyglutamine Length Determines Timing of Huntington’s Disease Onset
Lee, J.-M., Correia, K., Loupe, J., Kim, K.-H., Barker, D., Hong, E. P., Chao, M. J., Long, J. D., Lucente, D., Vonsattel, J. P. G., et al. (2019) · Cell · doi:10.1016/j.cell.2019.06.036 · Cited by 538
Self-citationPinto, R. M., Dragileva, E., Kirby, A., Lloret, A., Lopez, E., St. Claire, J., Panigrahi, G. B., Hou, C., Holloway, K., Gillis, T., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003930 · Cited by 250
“Importantly, we find that the MutL c components, MLH1 and MLH3, are as critical to somatic Hdh Q111 CAG expansion as the MutS b components MSH2 and MSH3 [18,19], suggesting that MutL c and MutS b are involved in the same pathway that promotes CAG/CTG expansion.”
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Metadata
- Authors
- Wheeler, V. C.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-02-01
- Volume
- 12
- Issue
- 3
- Pages
- 273-281
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2113629413
- Cited by
- 231
- References
- 6
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Open access
- closed
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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