title: Juvenile megaesophagus in PKCα-deficient mice is associated with an increase in the segment of the distal esophagus lined by smooth muscle cells.
abstract: Megaesophagus in mice has been associated with several genetic defects. In the present study we expand the range of genes associated with esophageal function and morphology by protein kinase C alpha (PKCα). PKCα-deficient mice showed a six times increased prevalence of megaesophagus at the age of 9-10 weeks compared to wild-type animals. In contrast, in a restricted number of 14-month-old animals of both genotypes a similar prevalence of megaesophagus was found. Megaesophagus was associated with an increased portion of the distal esophagus lined by smooth muscle cells. Achalasia-like degeneration or loss of neuronal cells, inflammation or fibrosis was not present in any of the animals. The results of the study therefore suggest that PKCα expression is associated with a delayed replacement of embryonic smooth muscle by skeletal muscle at the distal esophagus and consecutive megaesophagus in young mice, which, however, is not present at the same prevalence at an advanced age.
authors.affiliation: Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin, Berlin, Germany. Electronic address: elena-ariane.noe@charite.de.
authors.forename: Elena
authors.initials: E
authors.lastname: Noe
authors.affiliation: Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Tabeling
authors.affiliation: Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Jan-Moritz
authors.initials: JM
authors.lastname: Doehn
authors.affiliation: Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Naujoks
authors.affiliation: Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Opitz
authors.affiliation: Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hippenstiel
authors.affiliation: Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Witzenrath
authors.affiliation: Department of Veterinary Pathology, College of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Klopfleisch
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D004931:Esophageal Achalasia / Q000235:genetics* / Q000473:pathology*; D049630:Esophageal Sphincter, Lower / Q000473:pathology; D004947:Esophagus / Q000254:growth & development / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000473:pathology*; D051571:Protein Kinase C-alpha / Q000172:deficiency*
chemical_list: D000199:Actins; C544013:alpha-smooth muscle actin, mouse; C496630:Prkca protein, mouse; D051571:Protein Kinase C-alpha
keywords: Achalasia; Lower esophageal sphincter; Megaesophagus; Smooth muscle cells