Heightened susceptibility to chronic gastritis, hyperplasia and metaplasia in Kcnq1 mutant mice.
Increased susceptibility to gastric cancer has been associated with a wide range of host genetic and environmental factors, including Helicobacter pylori infection. Helicobacter pylori infection is postulated to initiate a progression through atrophic gastritis, metaplasia and dysplasia to cancer, and has been associated with reduction of acid output and dysregulation of stomach mucins. Here, we present the characterization of two mouse lines carrying mutant alleles of the gene encoding the Kcnq1 potassium channel, which very rapidly establish chronic gastritis in a pathogen-exposed environment. These mice develop gastric hyperplasia, hypochlorhydria and mucin dysregulation independent of infection. Metaplasia, dysplasia and pre-malignant adenomatous hyperplasia of the stomach have been observed in these Kcnq1 mutant mice, also independent of infection. The data presented here suggest that Kcnq1 mutant mice can be used both as an efficient model for the development of atrophic gastritis after infection and to determine the processes during the later stages of progression to gastric cancer independent of infection. Thus, Kcnq1 mutant mice are a powerful new tool for investigating the connection between acid balance, Helicobacter infection and mucin disruption in the progression to gastric cancer.
Elso
Colleen M
CM
Lawrence Livermore Laboratory, Livermore, CA 94550, USA.
Lu
Xiaochen
X
Culiat
Cymbeline T
CT
Rutledge
Joe C
JC
Cacheiro
Nestor L A
NL
Generoso
Walderico M
WM
Stubbs
Lisa J
LJ
D000126:Achlorhydria / Q000209:etiology / Q000235:genetics / Q000473:pathology; D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000483:Alleles; D000818:Animals; D002908:Chronic Disease; D005260:Female; D005752:Gastric Mucins / Q000378:metabolism; D005756:Gastritis / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D006965:Hyperplasia; D051656:KCNQ Potassium Channels / Q000235:genetics*; D008297:Male; D008679:Metaplasia; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D009206:Myocardium / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D013316:Stria Vascularis / Q000473:pathology; D014178:Translocation, Genetic
D005752:Gastric Mucins; D051656:KCNQ Potassium Channels