Expression of the apolipoprotein E gene in the skin is controlled by a unique downstream enhancer

A distal enhancer that specifies apolipoprotein E gene expression in the sk in was identified and characterized by in situ hybridization in transgenic mice generated with constructs of the human apolipoprotein E/C-I/C-IV/C-II gene duster. Transgene constructs containing the enhancer expressed high le vels of apolipoprotein E mRNA in the germinative cell layer of the sebaceou s gland and in epithelial cells of the hair follicle root sheath. Apolipopr otein E mRNA was also detected in basal epithelial cells of the epidermis. Expression of the human apolipoprotein E transgene at these sites was speci fied by a unique 1.0 kb enhancer domain located 1.7 kb downstream of the ap olipoprotein E gene. No transgene expression was detected in skin epithelia l cells in transgenic mice when this enhancer was deleted from the apolipop rotein E gene cluster, The enhancer was used to construct a transgene expre ssion vector that faithfully directed a heterologous cDNA to the normal sit es of apolipoprotein E gene expression in epithelial cells of the skin.