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In vivo functional analysis of the mouse estrogen receptor gene promoter: A transgenic mouse model to study tissue-specific and developmental regulation of estrogen receptor gene transcription
- Source :
- Scopus-Elsevier
-
Abstract
- Understanding the molecular and morphological basis of estrogen responsiveness in the various tissues and organs that make up an adult organism and its onset during ontogenesis requires identification of the genetic controls that determine timed expression of the estrogen receptor (ER) gene in multiple cell types. With this goal in mind, we describe here the results of the functional analysis of the mouse (m) ER gene promoter, carried out in vivo in transgenic mice. The mER gene promoter was cloned and spliced to the coding sequence of the bacterial lacZ gene (fused to the nuclear localization signal of SV40 large T: nls-beta-GAL) and then stably reintegrated into the genome of mice. Analysis of beta-GAL mRNA and protein expression in multiple organs of both female and male transgenic animals was then performed. Results show that the transgenic mER promoter, much like the endogenous one, is active in several organs and tissues of adult female and male mice. The first 0.4 kilobases of 5'-flanking DNA (up to -364) are sufficient to direct widespread expression of the transgene in mouse organs. This indicates that genetic elements functional in various cell types are included in this segment. Furthermore, the first exon and intron of the mER gene are necessary to achieve sexually dimorphic expression of the transgene in neurons located at specific sites within the central nervous system. These mER promoter transgenic mice will be useful in mapping estrogen- responsive cell types under different physiological and pathological conditions in vivo, in defining ontogenesis of estrogen action in the mouse, and in studying the mechanisms that regulate ER gene transcription.
- Subjects :
- Genetically modified mouse
Male
Transgene
Restriction Mapping
Estrogen receptor
Gestational Age
Mice, Transgenic
Biology
Exon
Mice
Endocrinology
Genes, Reporter
Animals
RNA, Messenger
Transgenes
Cloning, Molecular
Promoter Regions, Genetic
Molecular Biology
Gene
Estrogen receptor beta
Brain
Gene Expression Regulation, Developmental
Promoter
General Medicine
beta-Galactosidase
Molecular biology
Receptors, Estrogen
Female
Estrogen receptor alpha
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Scopus-Elsevier
- Accession number :
- edsair.doi.dedup.....60eff8ca302b37bd2dee10e26bd29baf