Use of gene-manipulated mice in the study of erythropoietin gene expression.
Transcriptional regulation of animal genes has been classified into two major categories: tissue-specific and stress-inducible. Erythropoietin (EPO), an erythroid growth factor, plays a central role in the regulation of red blood cell production. In response to hypoxic and/or anemic stresses, Epo gene expression is markedly induced in kidney and liver; thus, the Epo gene has been used as a model for elucidating stress-inducible gene expression in animals. A key transcriptional regulator of the hypoxia response, hypoxia-inducible transcription factor (HIF), has been identified and cloned through studies on the Epo gene. Recently developed gene-modified mouse lines have proven to be a powerful means of exploring the regulatory mechanisms as well as the physiological significance of the tissue-specific and hypoxia-inducible expression of the Epo gene. In this chapter, several gene-modified mouse lines related to EPO and the EPO receptor are introduced, with emphasis placed on the examination of in vivo EPO activity, EPO function in nonhematopoietic tissues, EPO-producing cells in the kidney, and cis-acting regulatory elements for Epo gene expression. These in vivo studies of the Epo gene have allowed for a deeper understanding of transcriptional regulation operated in a tissue-specific and stress-inducible manner.
Suzuki
Norio
N
ERATO Environmental Response Project, Japan Science and Technology Agency, Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Obara
Naoshi
N
Yamamoto
Masayuki
M
D000818:Animals; D004921:Erythropoietin / Q000032:analysis / Q000235:genetics*; D015870:Gene Expression; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D014018:Tissue Distribution
D004921:Erythropoietin; D049452:Green Fluorescent Proteins