Mice lacking neurofibromin develop gastric hyperplasia.
Gastrointestinal (GI) neoplasms are among many manifestations of the genetic disease neurofibromatosis type 1 (NF1). However, the physiological and pathological functions of the Nf1 gene in the GI system have not been fully studied, possibly because of a lack of mouse models. In this study, we generated conditional knockout mice with Nf1 deficiency in the GI tract. These mice develop gastric epithelial hyperplasia and inflammation together with increased cell proliferation and apoptosis. The gastric phenotypes observed in these mutant mice seem to be the consequence of loss of Nf1 in gastric fibroblasts, resulting in paracrine hyperactivation of the ERK pathway in the gastric epithelium. These mice provide a useful model to study the pathogenesis of GI lesions in a subset of patients with NF1 and to investigate the role of the Nf1 gene in the development of GI neoplasms.
Lin
Lu
L
Department of Developmental Biology and Kent Waldrep Foundation Center for Basic Neuroscience Research on NerveGrowth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9133, USA.
Chen
Jian
J
Richardson
James A
JA
Parada
Luis F
LF
D000367:Age Factors; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D005756:Gastritis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016514:Genes, Neurofibromatosis 1; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics; D006965:Hyperplasia; D019426:Integrases / Q000235:genetics; D060850:LIM-Homeodomain Proteins; D051379:Mice; D018345:Mice, Knockout; D009456:Neurofibromatosis 1 / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D025542:Neurofibromin 1 / Q000172:deficiency* / Q000235:genetics; D019899:Paracrine Communication; D010641:Phenotype; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors; D015431:Weight Loss
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D025542:Neurofibromin 1; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D048049:Extracellular Signal-Regulated MAP Kinases; C045073:Cre recombinase; D019426:Integrases