The murine Y₁ receptor 5′ upstream sequence directs cell‐specific and developmentally regulated LacZ expression in transgenic mice CNS

Abstract

The Y1 receptor for neuropeptide Y (NPY) is highly expressed in mammalian CNS where it mediates the activation of several neurobiological functions. We have previously demonstrated that a 1.3-kb fragment upstream of the transcription initiation sites of the murine Y1 receptor gene is able to direct specific expression of reporter genes in neuronal cell cultures. In the present study transgenic mice harbouring this putative promoter region linked to the LacZ reporter gene were generated and analysed for temporal and spatial distribution. Ten transgenic lines expressed beta-galactosidase in the CNS but not in other organs such as heart, liver and kidney. Histochemical analysis of brain from adult transgenic mice showed specific expression of the transgene in specific brain regions with little variation. Four transgenic lines showed characteristic patterns of beta-galactosidase activity in the brain that are consistent with the expression of the endogenous gene. Prominent LacZ activity was present in several telencephalic and diencephalic structures, including deeper layers of cerebral cortex, amygdaloid complex, hippocampus, preoptic area, several thalamic and hypothalamic nuclei and habenula. The ontogeny analysis indicates that the LacZ expression agrees with the temporal expression pattern of rat Y1 receptor mRNA. These data demonstrate that the 1.3-kb upstream region of the murine Y1 receptor gene contains the cis acting elements required for establishing a CNS-restricted and developmental stage-specific pattern of expression in vivo. Moreover they provide further information on the distribution of this NPY subtype receptor in mammalian brain.

17β-Estradiol Stimulates Mouse Neuropeptide Y-Y₁ Receptor Gene Transcription by Binding to Estrogen Receptor Alpha in Neuroblastoma Cells

“…We have recently generated transgenic mouse lines carrying the Y 1 receptor gene promoter/ LacZ fusion gene and we demonstrated that this transgenic model can be used to quantify changes in Y1 receptor gene expression in specific brain regions, induced, for instance, by pharmacological treatments [26, 44]. The analysis of the effect of estradiol on Y 1 receptor gene expression in the different hypothalamic nuclei from Y 1 R/Lac Z transgenic mice should then provide important information on the mechanisms involved in the steroid regulation of the NPY-mediated transmission.…”

“…This DNA contains sufficient information to replicate the expression pattern of the endogenous Y 1 receptor gene in a CNS-restricted and developmental stage-specific manner in transgenic mice [25, 26]. Sequence analysis of this region revealed the presence of several potential responsive elements for known transcription factors, including three hemipalindromic estrogen-responsive elements (ERE) [27].…”

Changes in expression of the neuropeptide Y Y1 receptor gene in the medial amygdala of transgenic mice during pregnancy and after delivery

“…Adult female Y 1 R/LacZ mice from transgenic line 62 (body mass, 25–30 g) obtained from our breeding colony were used for the experiments (Oberto et al . 1998).…”

“…Expression of lacZ was analyzed by histochemical staining of coronal brain sections for β‐galactosidase activity, as previously described (Oberto et al . 1998).…”

Increased expression of the neuropeptide Y receptor Y1 gene in the medial amygdala of transgenic mice induced by long‐term treatment with progesterone or allopregnanolone

“…2000). We previously generated 10 independent transgenic mouse lines harbouring a fusion construct ( Y 1 R/LacZ ) that comprises the mouse Y 1 receptor gene promoter linked to the lacZ gene and whose expression pattern mimics that of the endogenous Y 1 receptor gene in a CNS‐restricted and developmental stage‐specific manner (Oberto et al . 1998).…”