Megaoesophagus in Rassf1a-null mice

Louise van der Weyden, Lisa Happerfield, Mark J Arends, David J Adams

Research output: Contribution to journalArticlepeer-review


Megaoesophagus, or oesophageal achalasia, is a neuromuscular disorder characterized by an absence of peristalsis and flaccid dilatation of the oesophagus, resulting in the retention of ingesta in the dilated segment. The aetiology and pathogenesis of idiopathic (or primary) megaoesophagus are still poorly understood and very little is known about the genetic causes of megaoesophagus in humans. Attempts to develop animal models of this condition have been largely unsuccessful and although the ICRC/HiCri strain of mice spontaneously develop megaoesophagus, the underlying genetic cause remains unknown. In this report, we show that aged Rassf1a-null mice have an enhanced susceptibility to megaoesophagus compared with wild-type littermates (approximately 20%vs. approximately 2% incidence respectively; P = 0.01). Histological examination of the dilated oesophaguses shows a reduction in the numbers of nerve cells (both ganglia and nerve fibres) in the myenteric plexus of the dilated mid and lower oesophagus that was confirmed by S100 immunohistochemistry. There was also a chronic inflammatory infiltrate and subsequent fibrosis of the myenteric plexus and the muscle layers. These appearances closely mimic the gross and histopathological findings in human cases of megaoesophagus/achalasia, thus demonstrating that this is a representative mouse model of the disease. Thus, we have identified a genetic cause of the development of megaoesophagus/achalasia that could be screened for in patients, and may eventually facilitate the development of therapies that could prevent further progression of the disease once it is diagnosed at an early stage.
Original languageEnglish
Pages (from-to)101-8
Number of pages8
JournalInternational Journal of Experimental Pathology
Issue number2
Publication statusPublished - Apr 2009


  • Animals
  • Disease Models, Animal
  • Esophageal Achalasia
  • Esophagus
  • Genetic Predisposition to Disease
  • Mice
  • Mice, Knockout
  • S100 Proteins
  • Tumor Suppressor Proteins


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