Reduction of Htt inclusion formation in strains of Saccharomyces cerevisiae deficient in certain DNA repair functions: a statistical analysis of phenotype.
Saccharomyces cerevisiae has been used as a model system to examine the aggregation of the huntingtin protein (Htt), a well-established marker in the pathology of the triplet expansion disorder Huntington's disease (HD). Several genetic backgrounds, such as Deltahsp104, have proven to be refractory to inclusion formation through a process yet to be fully elucidated. These results have prompted a wide-ranging search for other mutant strains that exhibit a lower level of Htt aggregation. A novel assay system in which Htt is expressed as a fusion protein containing eGFP enables an analysis of aggregation and the factors that suppress it. We have examined several strains that are devoid of certain mismatch repair genes and find that some of these support a reduced level of inclusion body formation. We apply a detailed and stringent statistical analysis to the results obtained for all yeast strains that exhibit a definable phenotype. Such analyses should be useful and applicable to other in vivo analyses of related phenomena.
Hu
Yiling
Y
Department of Biological Sciences, University of Delaware, Delaware Biotechnology Institute, 15 Innovation Way, Newark, DE 19711, USA.
Liu
Li
L
Kmiec
Eric B
EB
D020137:Base Pair Mismatch / Q000235:genetics; D001681:Biological Assay / Q000379:methods; D002478:Cells, Cultured; D004260:DNA Repair / Q000235:genetics*; D003627:Data Interpretation, Statistical; D015536:Down-Regulation / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D013045:Species Specificity
D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins