title: Polyglutamine and transcription: gene expression changes shared by DRPLA and Huntington's disease mouse models reveal context-independent effects.
abstract: Recent evidence indicates that transcriptional abnormalities may play an important role in the pathophysiology of polyglutamine diseases. In the present study, we have explored the extent to which polyglutamine-related changes in gene expression may be independent of protein context by comparing mouse models of dentatorubral-pallidoluysian atrophy (DRPLA) and Huntington's disease (HD). Microarray gene expression profiling was conducted in mice of the same background strain in which the same promoter was employed to direct the expression of full-length atrophin-1 or partial huntingtin transproteins (At-65Q or N171-82Q mice). A large number of overlapping gene expression changes were observed in the cerebella of At-65Q and N171-82Q mice. Six of the gene expression changes common to both huntingtin and atrophin-1 transgenic mice were also observed in the cerebella of mouse models expressing full-length mutant ataxin-7 or the androgen receptor. These results demonstrate that some of the gene expression effects of expanded polyglutamine proteins occur independently of protein context.
authors.affiliation: Center for Aging, Genetics and Neurodegeneration, Massachusetts General Hospital, Charlestown, MA 02129-4404, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Luthi-Carter
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Strand
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Hanson
authors.forename: Charles
authors.initials: C
authors.lastname: Kooperberg
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schilling
authors.forename: Albert R
authors.initials: AR
authors.lastname: La Spada
authors.forename: Diane E
authors.initials: DE
authors.lastname: Merry
authors.forename: Anne B
authors.initials: AB
authors.lastname: Young
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ross
authors.forename: David R
authors.initials: DR
authors.lastname: Borchelt
authors.forename: James M
authors.initials: JM
authors.lastname: Olson
mesh_terms: D000818:Animals; D000067719:Ataxin-7; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D020191:Myoclonic Epilepsies, Progressive / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D019680:Trinucleotide Repeat Expansion
chemical_list: C000593829:ATXN7 protein, human; D000067719:Ataxin-7; C000593831:Atxn7 protein, mouse; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D012333:RNA, Messenger; D011944:Receptors, Androgen; C095278:atrophin-1; C097188:polyglutamine