Mice overexpressing CD97 in intestinal epithelial cells provide a unique model for mammalian postnatal intestinal cylindrical growth

Mol Biol Cell. 2013 Jul;24(14):2256-68. doi: 10.1091/mbc.E13-04-0175. Epub 2013 May 15.


Postnatal enlargement of the mammalian intestine comprises cylindrical and luminal growth, associated with crypt fission and crypt/villus hyperplasia, respectively, which subsequently predominate before and after weaning. The bipartite adhesion G protein-coupled receptor CD97 shows an expression gradient along the crypt-villus axis in the normal human intestine. We here report that transgenic mice overexpressing CD97 in intestinal epithelial cells develop an upper megaintestine. Intestinal enlargement involves an increase in length and diameter but does not affect microscopic morphology, as typical for cylindrical growth. The megaintestine is acquired after birth and before weaning, independent of the genotype of the mother, excluding altered availability of milk constituents as driving factor. CD97 overexpression does not regulate intestinal growth factors, stem cell markers, and Wnt signaling, which contribute to epithelial differentiation and renewal, nor does it affect suckling-to-weaning transition. Consistent with augmented cylindrical growth, suckling but not adult transgenic mice show enlarged crypts and thus more crypt fissions caused by a transient increase of the crypt transit-amplifying zone. Intestinal enlargement by CD97 requires its seven-span transmembrane/cytoplasmic C-terminal fragment but not the N-terminal fragment binding partner CD55. In summary, ectopic expression of CD97 in intestinal epithelial cells provides a unique model for intestinal cylindrical growth occurring in breast-fed infants.

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Animals, Suckling / physiology
  • CD55 Antigens / genetics
  • CD55 Antigens / metabolism
  • Cell Proliferation
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism
  • Female
  • Gene Expression*
  • Humans
  • Intestinal Mucosa / cytology*
  • Intestinal Mucosa / metabolism
  • Intestine, Small / cytology*
  • Intestine, Small / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Receptors, G-Protein-Coupled
  • Weaning


  • Adgre5 protein, mouse
  • CD55 Antigens
  • Membrane Glycoproteins
  • Receptors, G-Protein-Coupled