Phenotypes Associated with This Genotype

Genotype
MGI:5308013

• Allelic Composition: Tg(ED-L2-IL1RN/IL1B)#Tcw/?
• Genetic Background: B6.Cg-Tg(ED-L2-IL1RN/IL1B)#Tcw

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

digestive/alimentary system

abnormal digestive system morphology ( J:180282 )

• at 6 months of age profound epithelial hyperplasia is seen in the squamocolumnar junction

• at 12-15 months of age, 90% of mice display severe columnar metaplasia with mucus producing cells in the squamocolumnar junction

• treatment with 0.2% deoxycholate accelerates the development of Barrett-like metaplasia in the squamocolumnar junction

abnormal esophagus morphology ( J:180282 )

• at 20-22 months of age about 20% of mice develop high-grade dysplasia or intramucosal esophageal adenocarcinoma

• at 20-22 months of age lesions are grossly visible within the distal end of the esophagus

• mutant esophagi show circumferential erythema and edema with inflammatory exudates compared to the normal esophagus and changes are made more severe by treatment with 0.2% deoxycholate

• expansion of gastric cardia progenitor cells in the esophagus over time

enlarged esophagus ( J:180282 )

• markedly thickened

abnormal forestomach morphology ( J:180282 )

• markedly thickened with a mix of acute and chronic inflammatory infiltrate

abnormal digestive system physiology ( J:180282 )

• markedly thickened forestomach with a mix of acute and chronic inflammatory infiltrate

• increase in proliferation in the esophageal basal compartment

esophageal inflammation ( J:180282 )

• mix of acute and chronic inflammatory infiltrate

• treatment with 0.2% deoxycholate induced more severe esophagitis with inflammatory infiltrates in mutant mice compared to wild-type controls

neoplasm

increased incidence of tumors by chemical induction ( J:180282 )

• mice treated with 0.2% deoxycholate and N-methyl-N-nitrosourea show increased esophageal tumor development compared to wild-type controls

increased adenocarcinoma incidence ( J:180282 )

• at 20-22 months of age about 20% of mice develop high-grade dysplasia or intramucosal esophageal adenocarcinoma

• during the stepwise progression to cancer there is a gradual increase in alpha SMA+ stromal myofibroblasts and increasing stroma global hypomethylation

immune system

enlarged spleen ( J:180282 )

abnormal interleukin level ( J:180282 )

• elevated IL6 in the tongue, esophagus, and forestomach but not in the stomach

increased circulating interleukin-6 level ( J:180282 )

increased inflammatory response ( J:180282 )

• mix of acute and chronic inflammatory infiltrate in the forestomach

• at 6 months of age moderate inflammation is seen in the squamocolumnar junction

esophageal inflammation ( J:180282 )

• mix of acute and chronic inflammatory infiltrate

• treatment with 0.2% deoxycholate induced more severe esophagitis with inflammatory infiltrates in mutant mice compared to wild-type controls

homeostasis/metabolism

abnormal interleukin level ( J:180282 )

• elevated IL6 in the tongue, esophagus, and forestomach but not in the stomach

increased circulating interleukin-6 level ( J:180282 )

increased incidence of tumors by chemical induction ( J:180282 )

• mice treated with 0.2% deoxycholate and N-methyl-N-nitrosourea show increased esophageal tumor development compared to wild-type controls

growth/size/body

enlarged esophagus ( J:180282 )

• markedly thickened

weight loss ( J:180282 )

• at 20-22 months, associated with gross esophageal lesions

enlarged spleen ( J:180282 )

hematopoietic system

enlarged spleen ( J:180282 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Barrett's esophagus		DOID:9206	OMIM:614266	J:180282
esophageal cancer		DOID:5041	OMIM:133239	J:180282