Topo II alpha reporter mice reveal proliferative regions in the epidermis and small intestine.
We investigated topoisomerase II alpha promoter activity in epithelia. In confluent human keratinocytes the promoter (-557 to+90 bp) was upregulated by oncogenic Ras. In transgenic mice expressing GFP via the promoter, GFP expression in undamaged epidermis was confined to growing hair follicles. GFP was also expressed in intestinal crypts. GFP expression was upregulated in epidermis following wounding or phorbol ester treatment. In each situation GFP expression correlated with high endogenous topoisomerase II alpha expression and high proliferation. The mice therefore provide a useful model for non-invasive imaging of regions of high proliferation in normal or damaged epidermis.
Li
Elizabeth R
ER
Keratinocyte Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
Watt
Fiona M
FM
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D000078404:Epidermal Cells; D004817:Epidermis / Q000737:chemistry / Q000187:drug effects; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D018859:Hair Follicle / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007421:Intestine, Small / Q000737:chemistry / Q000166:cytology*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010703:Phorbol Esters / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012867:Skin / Q000293:injuries; D014945:Wound Healing / Q000235:genetics*
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D010703:Phorbol Esters; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D004250:DNA Topoisomerases, Type II