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opment of esophageal adenocarcinoma (i.e., 50%), only 4/12 mice

survived after 24 weeks of observation. Unfortunately, the applica-

bility of this model is limited by the short lifespan of p53 knockout

mice [ 18 ]. Others have reported performing surgery (esophagoje-

junostomy) in p27 knockout mice treated with carcinogens and

DgER [ 11 , 19 ]. Ellis et al. showed that 23.3% of mice developed

esophageal adenocarcinoma after 18–20 weeks of observation

[ 19 ]. In addition, Lechpammer et al. used the same model and

found an incidence of esophageal adenocarcinoma of 32% after

20 weeks of observation [ 11 ]. Esophageal adenocarcinoma induc-

tion methods and the associated incidence rates of esophageal ade-

nocarcinoma are summarized in Table 1.

In 2012, Quante et al. [ 20 ] reported a genetic mouse model

of Barrett’s esophagus and esophageal adenocarcinoma without

surgical intervention. They overexpressed human interleukin-1β in

the esophagus and squamous forestomach mucosa of mice using

Epstein–Barr virus promoter. All ten mice developed esophagitis

by 6 months of age, and 9/10 mice went on to develop Barrett’s

esophagus at 12–15 months. Of the nine mice used in this model,

two developed high-grade dysplasia or esophageal adenocarcinoma

at 20–22 months. The development of Barrett’s esophagus and

esophageal adenocarcinoma was accelerated in the mice whose

drinking water was treated with bile acid (0.2% deoxycholic acid).

Furthermore, bile acid combined with carcinogens significantly

accelerated Barrett’s esophagus and esophageal adenocarcinoma.

Table 1
Surgical procedures and resultant esophageal adenocarcinoma in mice

Study, year Surgical procedure

Genetic

modification

Carcinogen

used

EAC

incidence

Study duration

(weeks)

Fein et al.

(1999) [ 10 ]

Esophagojejunostomy

with gastrectomy

p53 knockout None 50% 24

Ellis et al.

(2001) [ 19 ]

Esophagojejunostomy None MBN 6% 18–20

p27 knockout MBN 20% 18–20

Lechpammer

et al. (2005)

[ 11 ]

Esophagojejunostomy p27 knockout MBN 32% 20

Hao et al.

(2009) [ 18 ]

Esophagogastroduodenal

anastomosis with/

without gastrectomy

p53A135V

or

INK4a/Arf+/−

None 0% 20

Quante et al.

(2012) [ 20 ]

None L2-IL-1β None 22.2% 86–94

Abbreviations: EAC esophageal adenocarcinoma, MBN N-methyl-N-benzylnitrosamine

Reflux Mouse Models in Esophageal Adenocarcinoma