BACKGROUND AND AIMS: Mice lacking epidermal growth factor (EGF), transforming growth factor alpha, and amphiregulin were used to identify roles for these EGF receptor (EGF-R) ligands in gastrointestinal development and mucosal integrity. METHODS: Gastrointestinal tract development was examined in knockout mice and correlated with expression of EGF-R protein and EGF family members throughout the gut. Crossfostering experiments addressed roles of maternal- and neonatal-derived ligands in pup growth and intestinal development. Cysteamine-induced ulceration in EGF(-/-) mice was used to examine its role in mucosal cytoprotection. RESULTS: Neonatal mice lacking all 3 ligands were growth retarded, even when reared by wild-type dams; conversely, lack of maternal ligands transiently impaired wild-type pup growth. Triple null neonates displayed spontaneous duodenal lesions, and ileal villi were truncated and fragile with reduced cellular proliferation in the crypts. However, maturation of digestive enzymes was unaffected. Adult EGF(-/-) mice displayed more severe lesions in response to cysteamine treatment compared with wild-type counterparts, although triple null mice were not more susceptible to dextran sulfate sodium-induced colitis, suggesting a differential role for these ligands in the injury response. CONCLUSIONS: EGF-R ligands are required for development and mucosal maintenance in mouse small intestine. Both maternal and neonatal sources of growth factors are required for optimal pup growth.
BACKGROUND AND AIMS: Mice lacking epidermal growth factor (EGF), transforming growth factor alpha, and amphiregulin were used to identify roles for these EGF receptor (EGF-R) ligands in gastrointestinal development and mucosal integrity. METHODS: Gastrointestinal tract development was examined in knockout mice and correlated with expression of EGF-R protein and EGF family members throughout the gut. Crossfostering experiments addressed roles of maternal- and neonatal-derived ligands in pup growth and intestinal development. Cysteamine-induced ulceration in EGF(-/-) mice was used to examine its role in mucosal cytoprotection. RESULTS: Neonatal mice lacking all 3 ligands were growth retarded, even when reared by wild-type dams; conversely, lack of maternal ligands transiently impaired wild-type pup growth. Triple null neonates displayed spontaneous duodenal lesions, and ileal villi were truncated and fragile with reduced cellular proliferation in the crypts. However, maturation of digestive enzymes was unaffected. Adult EGF(-/-) mice displayed more severe lesions in response to cysteamine treatment compared with wild-type counterparts, although triple null mice were not more susceptible to dextran sulfate sodium-induced colitis, suggesting a differential role for these ligands in the injury response. CONCLUSIONS:EGF-R ligands are required for development and mucosal maintenance in mouse small intestine. Both maternal and neonatal sources of growth factors are required for optimal pup growth.
Authors: Katharina Brandl; Lei Sun; Christina Neppl; Owen M Siggs; Sylvain M Le Gall; Wataru Tomisato; Xiaohong Li; Xin Du; Daniela N Maennel; Carl P Blobel; Bruce Beutler Journal: Proc Natl Acad Sci U S A Date: 2010-11-01 Impact factor: 11.205
Authors: Hiromitsu Hatakeyama; Haixia Cheng; Pamela Wirth; Ashley Counsell; Samuel R Marcrom; Carey Burton Wood; Paula R Pohlmann; Jill Gilbert; Barbara Murphy; Wendell G Yarbrough; Deric L Wheeler; Paul M Harari; Yan Guo; Yu Shyr; Robbert J Slebos; Christine H Chung Journal: PLoS One Date: 2010-09-13 Impact factor: 3.240
Authors: Leslie F Jackson; Ting Hu Qiu; Susan W Sunnarborg; Aileen Chang; Chunlian Zhang; Cam Patterson; David C Lee Journal: EMBO J Date: 2003-06-02 Impact factor: 11.598
Authors: Daekee Lee; R Scott Pearsall; Sanjoy Das; Sudhansu K Dey; Virginia L Godfrey; David W Threadgill Journal: Mol Cell Biol Date: 2004-10 Impact factor: 4.272