Intestinal maturation in mice lacking CCAAT/enhancer-binding protein α (C/EPBα)

In rodents, there is a surge of intestinal expression of CCAAT/ enhancer-binding protein alpha (C/EBP alpha) in the late fetal phase just before morphological maturation and the onset of expression of numerous epithelial genes. To investigate directly the hypothesis that C/EBP alpha 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 genotype were observed on mucosal architecture or on the size of the proliferative zone in the intestinal crypts, Likewise, the mRNA levels for the glucose transporter 2 (GLUT2), intestinal and liver fatty acid-binding proteins, and apolipoprotein A-IV in newborn intestine were similar in all genotypes. Paradoxically, Na+/glucose co-transporter (SGLT1), lactase phlorizin-hydrolase and apolipoprotein B mRNAs were more abundant in the C/EBP alpha-deficient animals. In wild-type intestines, C/EBP beta and C/EBP delta mRNAs were detectable throughout the late fetal period and increased toward term in parallel with C/EBP alpha mRNA. In newborn intestine, there was no compensatory up-regulation of these isoforms in the C/EBP alpha-deficient mice. We conclude that C/EBP alpha has no essential role in morphological maturation of the intestine, the pattern of proliferation of the epithelium, or the onset of expression of this cluster of epithelial mRNAs. However, since other C/EBP isoforms are present in the developing intestine, it is possible that there is a generic requirement for a member of the C/EBP family.