Huntington's disease (HD) is a progressive neurodegenerative disorder caused by trinucleotide repeat (TNR) expansions. We show here that somatic TNR expansions are significantly reduced in several organs of R6/1 mice lacking exon 2 of Nei-like 1 (Neil1) (R6/1/Neil1(-/-)), when compared with R6/1/Neil1(+/+) mice. Somatic TNR expansion is measured by two different methods, namely mean repeat change and instability index. Reduced somatic expansions are more pronounced in male R6/1/Neil1(-/-) mice, although expansions are also significantly reduced in brain regions of female R6/1/Neil1(-/-) mice. In addition, we show that the lack of functional Neil1 significantly reduces germline expansion in R6/1 male mice. In vitro, purified human NEIL1 protein binds and excises 5-hydroxycytosine in duplex DNA more efficiently than in hairpin substrates. NEIL1 excision of cytosine-derived oxidative lesions could therefore be involved in initiating the process of TNR expansion, although other DNA modifications might also contribute. Altogether, these results imply that Neil1 contributes to germline and somatic HD CAG repeat expansion.
Pubmed ID: 22914735 RIS Download
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Genotyping software package that provides DNA sizing and quality allele calls for all Applied Biosystems electrophoresis-based genotyping systems. GeneMapper specializes in multiapplication functionality, including amplified fragment length polymorphism, loss of heterozygosity, microsatellite, and SNP genotyping analysis. The software provides remote auto-analysis and command line operation, and allows for multiuser, client-server deployment.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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