title: Mice overexpressing CD97 in intestinal epithelial cells provide a unique model for mammalian postnatal intestinal cylindrical growth.
abstract: 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.
authors.affiliation: Department of Surgery, Research Laboratories, University of Leipzig, 04103 Leipzig, Germany. gabriela.aust@medizin.uni-leipzig.de
authors.forename: Gabriela
authors.initials: G
authors.lastname: Aust
authors.forename: Christiane
authors.initials: C
authors.lastname: Kerner
authors.forename: Susann
authors.initials: S
authors.lastname: Gonsior
authors.forename: Doreen
authors.initials: D
authors.lastname: Sittig
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schneider
authors.forename: Peter
authors.initials: P
authors.lastname: Buske
authors.forename: Markus
authors.initials: M
authors.lastname: Scholz
authors.forename: Norman
authors.initials: N
authors.lastname: Dietrich
authors.forename: Sindy
authors.initials: S
authors.lastname: Oldenburg
authors.forename: Olga N
authors.initials: ON
authors.lastname: Karpus
authors.forename: Jörg
authors.initials: J
authors.lastname: Galle
authors.forename: Salah
authors.initials: S
authors.lastname: Amasheh
authors.forename: Jörg
authors.initials: J
authors.lastname: Hamann
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling / Q000502:physiology; D018958:CD55 Antigens / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D043562:Receptors, G-Protein-Coupled; D014886:Weaning
chemical_list: C490633:Adgre5 protein, mouse; D018958:CD55 Antigens; D008562:Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled