Comt1 genotype and expression predicts anxiety and nociceptive sensitivity in inbred strains of mice.
Genes Brain Behav
; 9(8): 933-46, 2010 Nov.
Article
em En
| MEDLINE
| ID: mdl-20659173
ABSTRACT
Catechol-O-methyltransferase (COMT) is a ubiquitously expressed enzyme that maintains basic biologic functions by inactivating catechol substrates. In humans, polymorphic variance at the COMT locus has been associated with modulation of pain sensitivity and risk for developing psychiatric disorders. A functional haplotype associated with increased pain sensitivity was shown to result in decreased COMT activity by altering mRNA secondary structure-dependent protein translation. However, the exact mechanisms whereby COMT modulates pain sensitivity and behavior remain unclear and can be further studied in animal models. We have assessed Comt1 gene expression levels in multiple brain regions in inbred strains of mice and have discovered that Comt1 is differentially expressed among the strains, and this differential expression is cis-regulated. A B2 short interspersed nuclear element (SINE) was inserted in the 3'-untranslated region (3'-UTR) of Comt1 in 14 strains generating a common haplotype that correlates with gene expression. Experiments using mammalian expression vectors of full-length cDNA clones with and without the SINE element show that strains with the SINE haplotype (+SINE) have greater Comt1 enzymatic activity. +SINE mice also exhibit behavioral differences in anxiety assays and decreased pain sensitivity. These results suggest that a haplotype, defined by a 3'-UTR B2 SINE element, regulates Comt1 expression and some mouse behaviors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ansiedade
/
Dor
/
Catecol O-Metiltransferase
/
Limiar da Dor
/
Hipocampo
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Genes Brain Behav
Ano de publicação:
2010
Tipo de documento:
Article