Analysis of the Human Ferrochelatase Promoter in Transgenic Mice
作者： Scott T. Magness , Antonio Tugores , Edward S. Diala , David A. Brenner
DOI: 10.1182/BLOOD.V92.1.320.413K25_320_328
关键词: Regulation of gene expression 、 Molecular biology 、 Biology 、 Gene 、 Transgene 、 Genetically modified mouse 、 Northern blot 、 DNase I hypersensitive site 、 Erythropoiesis 、 Ferrochelatase
摘要: Ferrochelatase catalyzes the chelation of ferrous iron and protoporphyrin to form heme. It is expressed as a housekeeping gene in all cells, but upregulated during erythropoiesis. activity deficient inherited disease protoporphyria result heterogeneous mutations. Although human ferrochelatase transcribed from single promoter both nonerythroid erythroid previous studies using transient transfection assays failed demonstrate erythroid-specific increased expression 4.0 kb containing cis-elements, GATA NF-E2. The present study analyzes vivo regulation provide insights into mechanism its enhancement. Transgenic (TG) mouse lines were generated which luciferase reporter was driven by either 150-bp minimal (-0.15 TG) or extended 5' upstream region (-4.0 TG). Expression -4.0 TG transgene generally consistent with endogenous embryonic development tissues demonstrated Northern blotting mRNA situ hybridization. at higher level than -0.15 tissues, including extramedullary erythropoiesis induced n-acetylphenylhydrazine injection. enhanced correlates appearance DNase I hypersensitive site flanking transgene. Therefore, context chromosomal integration, necessary sufficient confer high levels tissue.
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