Epidermal Growth Factor and Glucagon Receptors in Mice Homozygous for a Lethal Chromosomal Deletion

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 80; no. 17; pp. 5379 - 5382
• Main Authors: Shaw, Phyllis A., Gluecksohn-Waelsch, Salome
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01.09.1983; National Acad Sciences
• Subjects: Albinism; Animals; Cell membranes; Cells; chromosome 7; Chromosome Deletion; epidermal growth factor; Epidermal Growth Factor - metabolism; ErbB Receptors; Genes, Lethal; glucagon; Glucagon - metabolism; Glucagon receptors; Hepatocytes; Homozygote; Homozygotes; Insulin; Kinetics; Liver; Liver - metabolism; Liver cells; Mice; Mice, Mutant Strains; Mutation; Myocardium - metabolism; Receptors; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, Glucagon
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.80.17.5379

The binding of epidermal growth factor (EGF) and of glucagon to their receptors has been examined in single-cell suspensions obtained from livers and other organs of newborn mice homozygous for a perinatally lethal deletion that includes the albino (c) locus on chromosome 7. Competition experiments with125I-labeled and nonradioactive EGF and Scatchard analysis of equilibrium binding data showed that hepatocytes from deletion homozygotes had only ≈ 20% of the number of specific EGF receptors present in cells from normal littermates. In contrast, EGF binding to single-cell suspensions from organs other than the liver was normal in deletion homozygotes. Similar results were obtained in competitive displacement experiments with125I-labeled and nonradioactive glucagon: hepatocytes from deletion mutants showed only ≈ 30% of the specific glucagon binding sites found in cells from normal littermates. As in the case of EGF, the decreased binding was due to decreased numbers of glucagon receptors per cell rather than alterations in receptor affinity, and glucagon binding to single-cell suspensions from organs other than the liver was normal in the deletion mutants. The reductions in numbers of EGF and glucagon receptors are liver-cell specific as are the previously described ultrastructural and biochemical abnormalities in these mutants. The significance of cell membrane integrity and hormone-receptor interactions in the control of normal liver cell differentiation is discussed.