INTESTINAL MATURATION IN MICE LACKING CCAAT ENHANCER-BINDING PROTEIN-ALPHA (C/EPB-ALPHA)/

In rodents, there is a surge of intestinal expression of CCAAT/ enhanc er-binding protein alpha (C/EBP alpha) in the late fetal phase just be fore morphological maturation and the onset of expression of numerous epithelial genes. To investigate directly the hypothesis that C/EBP al pha plays a causal role in the latter phenomena, we have assessed both structural and functional maturation in neonatal intestine from C/EBP alpha-null mice and their littermates. No effects of C/EBP alpha geno type were observed on mucosal architecture or on the size of the proli ferative zone in the intestinal crypts, Likewise, the mRNA levels for the glucose transporter 2 (GLUT2), intestinal and liver fatty acid-bin ding proteins, and apolipoprotein A-IV in newborn intestine were simil ar in all genotypes. Paradoxically, Na+/glucose co-transporter (SGLT1) , lactase phlorizin-hydrolase and apolipoprotein B mRNAs were more abu ndant in the C/EBP alpha-deficient animals. In wild-type intestines, C /EBP beta and C/EBP delta mRNAs were detectable throughout the late fe tal period and increased toward term in parallel with C/EBP alpha mRNA . In newborn intestine, there was no compensatory up-regulation of the se isoforms in the C/EBP alpha-deficient mice. We conclude that C/EBP alpha has no essential role in morphological maturation of the intesti ne, the pattern of proliferation of the epithelium, or the onset of ex pression of this cluster of epithelial mRNAs. However, since other C/E BP isoforms are present in the developing intestine, it is possible th at there is a generic requirement for a member of the C/EBP family.