Mouse Huntington's disease homolog mRNA levels: variation and allele effects.
Gene Expr
; 11(5-6): 221-31, 2004.
Article
en En
| MEDLINE
| ID: mdl-15200234
ABSTRACT
Huntington's disease homolog (Hdh) mRNA levels in mice with different Hdh alleles were measured. Brain Hdh mRNA levels varied up to threefold in genetically identical wild-type mice, indicating nongenetic factors influence Hdh expression. Striatal Hdh mRNA levels from an allele with a repeat expanded to 150 CAGs were diminished compared with wild-type and showed variation that might contribute to phenotypic variability in the Hdh(CAG)150 knock-in mouse model. To determine whether Hdh mRNA levels are tightly regulated, we assessed these levels in mice heterozygous for a deletion of the Hdh promoter. The loss of one allele reduced Hdh mRNA levels in most tissues, suggesting mechanisms to maintain Hdh mRNA levels are not in effect and should not impede therapies designed to destroy mutant huntingtin mRNA. Finally, we found a correlation between tissue mRNA levels and the susceptibility of the Hdh locus to Cre-mediated deletion. The two tissues with the highest levels of Hdh mRNA, testes and brain, were the only tissues susceptible to Cre-mediated recombination between loxP sites at Hdh locus. In contrast, the same Cre-expressing line caused recombination in every tissue for loxP sites at another genomic location. The pattern of Cre susceptibility at Hdh suggests a correlation between chromatin accessibility and high levels of Hdh expression in testes and brain.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Proteínas Nucleares
/
Enfermedad de Huntington
/
Alelos
/
Proteínas del Tejido Nervioso
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Gene Expr
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2004
Tipo del documento:
Article
País de afiliación:
Estados Unidos