RGD Reference Report - Differential D1 and D2 receptor-mediated effects on immediate early gene induction in a transgenic mouse model of Huntington's disease. - Rat Genome Database

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Differential D1 and D2 receptor-mediated effects on immediate early gene induction in a transgenic mouse model of Huntington's disease.

Authors: Spektor, BS  Miller, DW  Hollingsworth, ZR  Kaneko, YA  Solano, SM  Johnson, JM  Penney JB, JR  Young, AB  Luthi-Carter, R 
Citation: Spektor BS, etal., Brain Res Mol Brain Res. 2002 Jun 15;102(1-2):118-28.
RGD ID: 10395281
Pubmed: PMID:12191502   (View Abstract at PubMed)

The diminished expression of D1 and D2 dopamine receptors is a well-documented hallmark of Huntington's disease (HD), but relatively little is known about how these changes in receptor populations affect the dopaminergic responses of striatal neurons. Using transgenic mice expressing an N-terminal portion of mutant huntingtin (R6/2 mice), we have examined immediate early gene (IEG) expression as an index of dopaminergic signal transduction. c-fos, jun B, zif268, and N10 mRNA levels and expression patterns were analyzed using quantitative in situ hybridization histochemistry following intraperitoneal administration of selective D1 and D2 family pharmacological agents (SKF-82958 and eticlopride). Basal IEG levels were generally lower in the dorsal subregion of R6/2 striata relative to wild-type control striata at 10-11 weeks of age, a finding in accord with previously reported decreases in D1 and adenosine A2A receptors. D2-antagonist-stimulated IEG expression was significantly reduced in the striata of transgenic animals. In contrast, D1-agonist-induced striatal R6/2 IEG mRNA levels were either equivalent or significantly enhanced relative to control levels, an unexpected result given the reduced level of D1 receptors in R6/2 animals. Understanding the functional bases for these effects may further elucidate the complex pathophysiology of Huntington's disease.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Huntington's disease  ISOEgr1 (Mus musculus)10395281; 10395281 RGD 
Huntington's disease  IEP 10395281 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Egr1  (early growth response 1)

Genes (Mus musculus)
Egr1  (early growth response 1)

Genes (Homo sapiens)
EGR1  (early growth response 1)


Additional Information