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Intestinal maturation in mice lacking CCAAT/enhancer-binding protein alpha (C/EPBalpha)
T J Oesterreicher1, L L Leeper, M J Finegold
1Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Insights
CCAAT/enhancer-binding protein alpha (C/EBPalpha) is not essential for intestinal development or epithelial gene expression in mice. However, other C/EBP family members may play a role in this process.
Area of Science:
- Developmental Biology
- Molecular Biology
- Gastroenterology
Background:
- CCAAT/enhancer-binding protein alpha (C/EBPalpha) expression surges in the late fetal rodent intestine.
- This surge precedes intestinal morphological maturation and epithelial gene expression onset.
Purpose of the Study:
- To investigate the causal role of C/EBPalpha in intestinal maturation and epithelial gene expression.
- To assess structural and functional maturation in C/EBPalpha-null mice neonates.
Main Methods:
- Comparative analysis of C/EBPalpha-null mice and littermates.
- Assessment of mucosal architecture and proliferative zone size.
- Quantification of specific epithelial gene mRNA levels (GLUT2, SGLT1, lactase, apolipoproteins).
Main Results:
- No significant differences in mucosal architecture or proliferative zone size were observed between genotypes.
- mRNA levels for GLUT2, intestinal/liver fatty acid-binding proteins, and apolipoprotein A-IV were similar.
- Paradoxically, SGLT1, lactase phlorizin-hydrolase, and apolipoprotein B mRNAs were higher in C/EBPalpha-deficient mice.
- No compensatory upregulation of C/EBPbeta and C/EBPdelta was found in knockout animals.
Conclusions:
- C/EBPalpha is not essential for intestinal morphological maturation, epithelial proliferation patterns, or the onset of specific epithelial gene expression.
- Other C/EBP family members might fulfill a generic requirement for intestinal development.
Abstract:
In rodents, there is a surge of intestinal expression of CCAAT/enhancer-binding protein alpha (C/EBPalpha) 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/EBPalpha plays a causal role in the latter phenomena, we have assessed both structural and functional maturation in neonatal intestine from C/EBPalpha-null mice and their littermates. No effects of C/EBPalpha 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/EBPalpha-deficient animals. In wild-type intestines, C/EBPbeta and C/EBPdelta mRNAs were detectable throughout the late fetal period and increased toward term in parallel with C/EBPalpha mRNA. In newborn intestine, there was no compensatory up-regulation of these isoforms in the C/EBPalpha-deficient mice. We conclude that C/EBPalpha 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.