Decreased expression of striatal signaling genes in a mouse model of Huntington's disease.
To understand gene expression changes mediated by a polyglutamine repeat expansion in the human huntingtin protein, we used oligonucleotide DNA arrays to profile approximately 6000 striatal mRNAs in the R6/2 mouse, a transgenic Huntington's disease (HD) model. We found diminished levels of mRNAs encoding components of the neurotransmitter, calcium and retinoid signaling pathways at both early and late symptomatic time points (6 and 12 weeks of age). We observed similar changes in gene expression in another HD mouse model (N171-82Q). These results demonstrate that mutant huntingtin directly or indirectly reduces the expression of a distinct set of genes involved in signaling pathways known to be critical to striatal neuron function.
Luthi-Carter
R
R
Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA,
Strand
A
A
Peters
N L
NL
Solano
S M
SM
Hollingsworth
Z R
ZR
Menon
A S
AS
Frey
A S
AS
Spektor
B S
BS
Penney
E B
EB
Schilling
G
G
Ross
C A
CA
Borchelt
D R
DR
Tapscott
S J
SJ
Young
A B
AB
Cha
J H
JH
Olson
J M
JM
D000262:Adenylyl Cyclases / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics*; D017403:In Situ Hybridization; D007249:Inflammation / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014793:Visual Cortex / Q000378:metabolism*
C086055:HTT protein, human; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D009687:Nuclear Proteins; D010455:Peptides; D012333:RNA, Messenger; C097188:polyglutamine; D000262:Adenylyl Cyclases; D002118:Calcium