Related Experiment Videos
Epidermal growth factor receptor in mice and men--any applications to clinical practice?
1Department of Pathology, University of Helsinki and Hospital for Children and Adolescents, Finland. paivi.miettinen@helsinki.fi
Abstract:
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.
Insights
Epidermal growth factor receptor (EGF-R) inactivation causes developmental defects in organs like the lungs and intestines, leading to postnatal lethality in mice. These findings offer insights into human prematurity complications.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- The epidermal growth factor receptor (EGF-R) is a key tyrosine kinase receptor involved in cellular growth and differentiation.
- EGF-R signaling is crucial for the development and maintenance of various epithelial tissues.
- Inactivation of EGF-R leads to distinct developmental phenotypes, impacting multiple organ systems.
Purpose of the Study:
- To investigate the consequences of EGF-R inactivation on embryonic and postnatal development.
- To characterize the specific organ defects arising from EGF-R deficiency.
- To explore the relevance of EGF-R function to human diseases, particularly those associated with prematurity.
Main Methods:
- Homologous recombination was used to generate EGF-R knockout mice (EGF-R -/-).
- Phenotypic analysis was performed on mice with varying degrees of EGF-R inactivation.
- Histological examination of affected organs, including lungs and intestines, was conducted.
Main Results:
- EGF-R inactivation resulted in phenotypes ranging from peri-implantation to postnatal lethality.
- Postnatal lethal phenotypes exhibited epithelial immaturity, respiratory failure due to impaired lung branching, and necrotizing enterocolitis-like intestinal lesions.
- Affected organs included skin, intestine, lung, kidney, mammary gland, pancreas, and prostate, consistent with EGF-R's role as an epithelial mitogen.
Conclusions:
- EGF-R is essential for the proper development of multiple organ systems, particularly those involving epithelial branching morphogenesis.
- The lung and intestinal phenotypes in EGF-R deficient mice resemble human respiratory distress syndrome, bronchopulmonary dysplasia, and necrotizing enterocolitis.
- While not the cause, impaired EGF-R function may exacerbate certain prematurity-associated diseases, suggesting potential therapeutic roles for EGF family members.