title: Gastroschisis in mice lacking aortic carboxypeptidase-like protein is associated with a defect in neuromuscular development of the eviscerated intestine.
abstract: Mice lacking aortic carboxypeptidase-like protein (ACLP) exhibit a gastroschisis (GS) like abdominal wall defect. The objectives of this study were to evaluate the pathophysiological features of GS in ACLP mice and to characterize the neuromuscular development of the eviscerated intestine (EI). ACLP mice were created by heterozygous mating from previously generated mice with targeted disruption of ACLP. Specimens were processed for H&E, and immunohistochemistry for smooth muscle cells [SMC, alpha-smooth muscle actin (alpha-SMA) antibody], interstitial cells of Cajal (ICC, c-kit-antibody), neural crest cells (NCC, Hox-b5-antibody), and enteric neurons (EN, PGP9.5-, alpha-internexin, and synaptophysin antibody). From 47 fetuses genotyped, 13 (27.7%) were wild type, 20 (42.5%) were heterozygous, and 14 (29.8%) were ACLP homozygous. In GS mice, expression of c-kit, Hox-b5, PGP-9.5, alpha-internexin, and synaptophysin were almost completely absent and only faint alpha-SMA expression was seen in the EI. In contrast, c-kit, Hox-b5, PGP9.5, alpha-internexin, synaptophysin, and alpha-SMA expression in intra-abdominal intestine in GS fetuses was the same as control intestine. The defect observed in ACLP mice closely resembles GS. Absence of ICC, NCC, EN, and immature differentiation of SMC supports an associated defect in neuromuscular development that is restricted to the EI.
authors.affiliation: The Center for Fetal Research, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Enrico
authors.initials: E
authors.lastname: Danzer
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Layne
authors.forename: Frederic
authors.initials: F
authors.lastname: Auber
authors.forename: Shincy
authors.initials: S
authors.lastname: Shegu
authors.forename: Portia
authors.initials: P
authors.lastname: Kreiger
authors.forename: Antoneta
authors.initials: A
authors.lastname: Radu
authors.forename: Maryann
authors.initials: M
authors.lastname: Volpe
authors.forename: N Scott
authors.initials: NS
authors.lastname: Adzick
authors.forename: Alan W
authors.initials: AW
authors.lastname: Flake
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002268:Carboxypeptidases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000033:anatomy & histology / Q000473:pathology; D020139:Gastroschisis / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D056885:Interstitial Cells of Cajal / Q000166:cytology / Q000378:metabolism; D007422:Intestines / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000002:abnormalities / Q000196:embryology / Q000294:innervation; D011247:Pregnancy; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C112918:Aebp1 protein, mouse; D015415:Biomarkers; D012097:Repressor Proteins; D002268:Carboxypeptidases