MOUSE DECAY-ACCELERATING FACTOR - SELECTIVE AND TISSUE-SPECIFIC INDUCTION BY ESTROGEN OF THE GENE ENCODING THE GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHORED FORM

Neonatal exposure of mice to estrogen (diethylstilbestrol) results in a high incidence (90%) of uterine tumor later in life. In an effort to screen for estrogen-regulated genes in the uterus of the neonatal mou se, we have isolated a murine homologue of the human decay-acceleratin g factor (DAF), a glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein and a member of the regulators of complement activation family of proteins that function to prevent autologous complement-medi ated tissue damage. The induced mouse DAF cDNA has a 64% sequence iden tity with the human counterpart at the nucleotide level and a 50% iden tity in the deduced amino acid sequence, It consists of 390 amino acid s and contains four short consensus repeats of internal homology chara cteristic of human DAF, It. also contains a hydrophobic C-terminal tha t most likely serves as a signal for GPI anchor attachment. Sequence c omparison with the recently reported mouse DAF cDNAs confirmed that th e estrogen-inducible gene corresponds to the mouse GPI DAF gene. The i nduction of mouse DAF by estrogen is tissue specific and can be mimick ed by the antiestrogen tamoxifen, Furthermore, the, regulation of uter ine DAF expression by estrogen is limited to the GPI DAF gene, The tra nsmembrane DAF gene is not expressed in the mouse uterus, either with or without estrogen stimulation, These results suggest that the two mo use DAF genes are differentially regulated, and that the GPI-anchored DAF may play important roles in estrogen responses and other physiolog ic or pathophysiologic processes of the female reproductive system.