Epidermal growth factor receptor in mice and men--any applications to clinical practice?
The epidermal growth factor receptor (EGF-R) is perhaps the best studied member of tyrosine kinase receptors. Its inactivation by homologous recombination results in three different phenotypes ranging from peri-implantation lethality to postnatal lethality. The mildest form of EGF-R inactivation leads to epithelial immaturity and postnatal death due to respiratory failure and necrotizing enterocolitis-like lesions in the intestine. The defects seen in this 'postnatal lethality phenotype' manifest in the classical EGF-responsive organs (skin, intestine) and organs undergoing branching morphogenesis during development (lung, kidney, mammary gland, pancreas and prostate), and thus accord with the concept of EGF family members being important epithelial mitogens. The respiratory failure of the EGF-R (-/-) mice results from impaired branching of the alveolar tree and leads to decreased surface for gas exchange. Overall, the lung phenotype bears similarity to respiratory distress syndrome and bronchopulmonary dysplasia--the most common complications of prematurity in humans. Intestinal changes seen in the EGF-R (-/-) mice vary in severity, the end-point being severe mucosal lesions and necroses. These findings resemble those seen in necrotizing enterocolitis of premature babies, a serious intestinal problem in the neonate. Although deficient EGF-R function is not the reason for these prematurity-associated diseases it may nevertheless exacerbate them. Potential usage of EGF transforming growth factor-alpha in clinical work is discussed.
Miettinen
P J
PJ
Department of Pathology, University of Helsinki and Hospital for Children and Adolescents, Finland. paivi.miettinen@helsinki.fi
D000818:Animals; D001940:Breast / Q000196:embryology; D001997:Bronchopulmonary Dysplasia / Q000209:etiology; D004761:Enterocolitis, Pseudomembranous / Q000209:etiology; D004848:Epithelium / Q000502:physiology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000209:etiology; D007422:Intestines / Q000196:embryology; D007668:Kidney / Q000196:embryology; D008168:Lung / Q000196:embryology; D008297:Male; D008321:Mammary Glands, Animal / Q000196:embryology; D051379:Mice; D009024:Morphogenesis; D010179:Pancreas / Q000196:embryology; D010641:Phenotype; D011467:Prostate / Q000196:embryology; D011650:Pulmonary Alveoli / Q000196:embryology; D011659:Pulmonary Gas Exchange; D011995:Recombination, Genetic; D012127:Respiratory Distress Syndrome, Newborn / Q000209:etiology; D012131:Respiratory Insufficiency / Q000209:etiology; D012867:Skin / Q000196:embryology; D016211:Transforming Growth Factor alpha / Q000627:therapeutic use
D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors