Megaesophagus in a Line of Transgenic Rats

A Model of Achalasia

J. Pang, T. M. Borjeson, S. Muthupalani, Rebecca Ducore, C. A. Carr, Y. Feng, M. P. Sullivan, V. Cristofaro, J. Luo, J. M. Lindstrom, J. G. Fox

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Megaesophagus is defined as the abnormal enlargement or dilatation of the esophagus, characterized by a lack of normal contraction of the esophageal walls. This is called achalasia when associated with reduced or no relaxation of the lower esophageal sphincter (LES). To date, there are few naturally occurring models for this disease. A colony of transgenic (Pvrl3-Cre) rats presented with megaesophagus at 3 to 4 months of age; further breeding studies revealed a prevalence of 90% of transgene-positive animals having megaesophagus. Affected rats could be maintained on a total liquid diet long term and were shown to display the classic features of dilated esophagus, closed lower esophageal sphincter, and abnormal contractions on contrast radiography and fluoroscopy. Histologically, the findings of muscle degeneration, inflammation, and a reduced number of myenteric ganglia in the esophagus combined with ultrastructural lesions of muscle fiber disarray and mitochondrial changes in the striated muscle of these animals closely mimic that seen in the human condition. Muscle contractile studies looking at the response of the lower esophageal sphincter and fundus to electrical field stimulation, sodium nitroprusside, and L-nitro-L-arginine methyl ester also demonstrate the similarity between megaesophagus in the transgenic rats and patients with achalasia. No primary cause for megaesophagus was found, but the close parallel to the human form of the disease, as well as ease of care and manipulation of these rats, makes this a suitable model to better understand the etiology of achalasia as well as study new management and treatment options for this incurable condition.

Original languageEnglish (US)
Pages (from-to)1187-1200
Number of pages14
JournalVeterinary Pathology
Volume51
Issue number6
DOIs
StatePublished - Nov 8 2014
Externally publishedYes

Fingerprint

megaesophagus
Transgenic Rats
Esophageal Achalasia
genetically modified organisms
rats
esophageal sphincter
Lower Esophageal Sphincter
esophagus
Esophagus
Muscles
liquid diet
muscles
striated muscle
Striated Muscle
disease models
Fluoroscopy
Nitroprusside
electric field
radiography
Transgenes

Keywords

  • achalasia
  • esophagus
  • imaging
  • immunohistochemistry
  • megaesophagus
  • muscle studies
  • Pvrl3
  • rat
  • ultrastructure

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Pang, J., Borjeson, T. M., Muthupalani, S., Ducore, R., Carr, C. A., Feng, Y., ... Fox, J. G. (2014). Megaesophagus in a Line of Transgenic Rats: A Model of Achalasia. Veterinary Pathology, 51(6), 1187-1200. https://doi.org/10.1177/0300985813519136

Megaesophagus in a Line of Transgenic Rats : A Model of Achalasia. / Pang, J.; Borjeson, T. M.; Muthupalani, S.; Ducore, Rebecca; Carr, C. A.; Feng, Y.; Sullivan, M. P.; Cristofaro, V.; Luo, J.; Lindstrom, J. M.; Fox, J. G.

In: Veterinary Pathology, Vol. 51, No. 6, 08.11.2014, p. 1187-1200.

Research output: Contribution to journalArticle

Pang, J, Borjeson, TM, Muthupalani, S, Ducore, R, Carr, CA, Feng, Y, Sullivan, MP, Cristofaro, V, Luo, J, Lindstrom, JM & Fox, JG 2014, 'Megaesophagus in a Line of Transgenic Rats: A Model of Achalasia', Veterinary Pathology, vol. 51, no. 6, pp. 1187-1200. https://doi.org/10.1177/0300985813519136
Pang J, Borjeson TM, Muthupalani S, Ducore R, Carr CA, Feng Y et al. Megaesophagus in a Line of Transgenic Rats: A Model of Achalasia. Veterinary Pathology. 2014 Nov 8;51(6):1187-1200. https://doi.org/10.1177/0300985813519136
Pang, J. ; Borjeson, T. M. ; Muthupalani, S. ; Ducore, Rebecca ; Carr, C. A. ; Feng, Y. ; Sullivan, M. P. ; Cristofaro, V. ; Luo, J. ; Lindstrom, J. M. ; Fox, J. G. / Megaesophagus in a Line of Transgenic Rats : A Model of Achalasia. In: Veterinary Pathology. 2014 ; Vol. 51, No. 6. pp. 1187-1200.
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