Molecular mechanism of change in serum alpha-fetoprotein concentration during neonatal development of analbuminemic rats.

Analbuminemic rats, which lack albumin synthesis in the liver, have been shown to have a defect in splicing of albumin mRNA precursors. Change in serum alpha-fetoprotein concentration during the neonatal period in these mutant rats was compared with change of their gene expression of albumin. In analbuminemic rats the serum alpha-fetoprotein concentration at birth was almost the same as that of normal rats, and its concentration gradually decreased to a nondetectable level within 3 to 4 weeks after birth, as in normal rats, without increase in serum albumin concentration. In spite of the absence of increase in serum albumin, increase in transcripts of the albumin gene was observed. The level of "albumin mRNA precursors" in nuclei of the liver was less than 0.05 ng/micrograms of nuclear RNA at birth, but increased to 1 ng/micrograms within 3 weeks after birth in normal rats. Although the extent of increase was less, a similar switch-on of the albumin gene was observed in analbuminemic rats in the developmental period. These data clearly indicated that even in analbuminemic rats, coordinated regulation of the alpha-fetoprotein and albumin genes took place at a transcriptional level during development.