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. 1996 Jun 1;97(11):2426–2432. doi: 10.1172/JCI118689

Reduced epidermal growth factor receptor expression in hypohidrotic ectodermal dysplasia and Tabby mice.

G A Vargas 1, E Fantino 1, C George-Nascimento 1, J J Gargus 1, H T Haigler 1
PMCID: PMC507327  PMID: 8647934

Abstract

Patients with hypohidrotic ectodermal dysplasia (HED) and Tabby (Ta) mice lack sweat glands and there is compelling evidence that these phenotypes are caused by mutations in the same highly conserved but unidentified X-linked gene. Previous studies showed that exogenous epidermal growth factor (EGF) reversed the Ta phenotype but the EGF status in HED patients has not been studied at all. Studies reported herein investigated the hypothesis that the EGF signaling pathway is involved in HED/Ta. Fibroblasts from HED patients had a two- to eightfold decrease in binding capacity for (125)I-labeled EGF, a decreased expression of the immunoreactive 170-kD EGF receptor (EGFR) protein, and a corresponding reduction in EGFR mRNA. Reduced expression of the EGFR also was observed in Ta fibroblasts and liver membranes. Other aspects of the EGF signaling pathway, including EGF concentration in urine and plasma, were normal in both HED patients and Ta mice. We propose that a decreased expression of the EGFR plays a causal role in the HED/Ta phenotype.

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Selected References

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  1. Carpenter G., Cohen S. 125I-labeled human epidermal growth factor. Binding, internalization, and degradation in human fibroblasts. J Cell Biol. 1976 Oct;71(1):159–171. doi: 10.1083/jcb.71.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Carpenter G., Cohen S. Epidermal growth factor. J Biol Chem. 1990 May 15;265(14):7709–7712. [PubMed] [Google Scholar]
  3. Carpenter G. Receptors for epidermal growth factor and other polypeptide mitogens. Annu Rev Biochem. 1987;56:881–914. doi: 10.1146/annurev.bi.56.070187.004313. [DOI] [PubMed] [Google Scholar]
  4. Clarke A., Phillips D. I., Brown R., Harper P. S. Clinical aspects of X-linked hypohidrotic ectodermal dysplasia. Arch Dis Child. 1987 Oct;62(10):989–996. doi: 10.1136/adc.62.10.989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Collins F. S. Positional cloning: let's not call it reverse anymore. Nat Genet. 1992 Apr;1(1):3–6. doi: 10.1038/ng0492-3. [DOI] [PubMed] [Google Scholar]
  6. Gates R. E., King L. E., Jr Calcium facilitates endogenous proteolysis of the EGF receptor-kinase. Mol Cell Endocrinol. 1982 Aug;27(3):263–276. doi: 10.1016/0303-7207(82)90093-4. [DOI] [PubMed] [Google Scholar]
  7. Gregory H., Holmes J. E., Willshire I. R. Urogastrone levels in the urine of normal adult humans. J Clin Endocrinol Metab. 1977 Oct;45(4):668–672. doi: 10.1210/jcem-45-4-668. [DOI] [PubMed] [Google Scholar]
  8. Haigler H. T., Maxfield F. R., Willingham M. C., Pastan I. Dansylcadaverine inhibits internalization of 125I-epidermal growth factor in BALB 3T3 cells. J Biol Chem. 1980 Feb 25;255(4):1239–1241. [PubMed] [Google Scholar]
  9. Haigler H. T., McKanna J. A., Cohen S. Direct visualization of the binding and internalization of a ferritin conjugate of epidermal growth factor in human carcinoma cells A-431. J Cell Biol. 1979 May;81(2):382–395. doi: 10.1083/jcb.81.2.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Haigler H. T., Schlaepfer D. D., Burgess W. H. Characterization of lipocortin I and an immunologically unrelated 33-kDa protein as epidermal growth factor receptor/kinase substrates and phospholipase A2 inhibitors. J Biol Chem. 1987 May 15;262(14):6921–6930. [PubMed] [Google Scholar]
  11. Hirata Y., Orth D. N. Concentrations of epidermal growth factor, nerve growth factor, and submandibular gland renin in male and female mouse tissue and fluids. Endocrinology. 1979 Dec;105(6):1382–1387. doi: 10.1210/endo-105-6-1382. [DOI] [PubMed] [Google Scholar]
  12. Jansson J. O., Ekberg S., Hoath S. B., Beamer W. G., Frohman L. A. Growth hormone enhances hepatic epidermal growth factor receptor concentration in mice. J Clin Invest. 1988 Dec;82(6):1871–1876. doi: 10.1172/JCI113804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kapalanga J., Blecher S. R. Effect of the X-linked gene Tabby (Ta) on eyelid opening and incisor eruption in neonatal mice is opposite to that of epidermal growth factor. Development. 1990 Feb;108(2):349–355. doi: 10.1242/dev.108.2.349. [DOI] [PubMed] [Google Scholar]
  14. Lillien L. Changes in retinal cell fate induced by overexpression of EGF receptor. Nature. 1995 Sep 14;377(6545):158–162. doi: 10.1038/377158a0. [DOI] [PubMed] [Google Scholar]
  15. Luetteke N. C., Phillips H. K., Qiu T. H., Copeland N. G., Earp H. S., Jenkins N. A., Lee D. C. The mouse waved-2 phenotype results from a point mutation in the EGF receptor tyrosine kinase. Genes Dev. 1994 Feb 15;8(4):399–413. doi: 10.1101/gad.8.4.399. [DOI] [PubMed] [Google Scholar]
  16. Luetteke N. C., Qiu T. H., Peiffer R. L., Oliver P., Smithies O., Lee D. C. TGF alpha deficiency results in hair follicle and eye abnormalities in targeted and waved-1 mice. Cell. 1993 Apr 23;73(2):263–278. doi: 10.1016/0092-8674(93)90228-i. [DOI] [PubMed] [Google Scholar]
  17. MacDermot K. D., Hultén M. Female with hypohidrotic ectodermal dysplasia and de novo (X;9) translocation. Clinical documentation of the AnLy cell line case. Hum Genet. 1990 May;84(6):577–579. doi: 10.1007/BF00210814. [DOI] [PubMed] [Google Scholar]
  18. Miettinen P. J., Berger J. E., Meneses J., Phung Y., Pedersen R. A., Werb Z., Derynck R. Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. Nature. 1995 Jul 27;376(6538):337–341. doi: 10.1038/376337a0. [DOI] [PubMed] [Google Scholar]
  19. Nanney L. B., Stoscheck C. M., King L. E., Jr, Underwood R. A., Holbrook K. A. Immunolocalization of epidermal growth factor receptors in normal developing human skin. J Invest Dermatol. 1990 Jun;94(6):742–748. doi: 10.1111/1523-1747.ep12874601. [DOI] [PubMed] [Google Scholar]
  20. Oka Y., Orth D. N. Human plasma epidermal growth factor/beta-urogastrone is associated with blood platelets. J Clin Invest. 1983 Jul;72(1):249–259. doi: 10.1172/JCI110964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pathak B. G., Gilbert D. J., Harrison C. A., Luetteke N. C., Chen X., Klagsbrun M., Plowman G. D., Copeland N. G., Jenkins N. A., Lee D. C. Mouse chromosomal location of three EGF receptor ligands: amphiregulin (Areg), betacellulin (Btc), and heparin-binding EGF (Hegfl). Genomics. 1995 Jul 1;28(1):116–118. doi: 10.1006/geno.1995.1116. [DOI] [PubMed] [Google Scholar]
  22. Saga K., Takahashi M. Immunoelectron microscopic localization of epidermal growth factor in the eccrine and apocrine sweat glands. J Histochem Cytochem. 1992 Feb;40(2):241–249. doi: 10.1177/40.2.1552167. [DOI] [PubMed] [Google Scholar]
  23. Sibilia M., Wagner E. F. Strain-dependent epithelial defects in mice lacking the EGF receptor. Science. 1995 Jul 14;269(5221):234–238. doi: 10.1126/science.7618085. [DOI] [PubMed] [Google Scholar]
  24. Starkey R. H., Orth D. N. Radioimmunoassay of human epidermal growth factor (urogastrone). J Clin Endocrinol Metab. 1977 Dec;45(6):1144–1153. doi: 10.1210/jcem-45-6-1144. [DOI] [PubMed] [Google Scholar]
  25. Thomas N. S., Chelly J., Zonana J., Davies K. J., Morgan S., Gault J., Rack K. A., Buckle V. J., Brockdorff N., Clarke A. Characterisation of molecular DNA rearrangements within the Xq12-q13.1 region, in three patients with X-linked hypohidrotic ectodermal dysplasia (EDA). Hum Mol Genet. 1993 Oct;2(10):1679–1685. doi: 10.1093/hmg/2.10.1679. [DOI] [PubMed] [Google Scholar]
  26. Threadgill D. W., Dlugosz A. A., Hansen L. A., Tennenbaum T., Lichti U., Yee D., LaMantia C., Mourton T., Herrup K., Harris R. C. Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. Science. 1995 Jul 14;269(5221):230–234. doi: 10.1126/science.7618084. [DOI] [PubMed] [Google Scholar]
  27. Tsutsumi O., Kurachi H., Oka T. A physiological role of epidermal growth factor in male reproductive function. Science. 1986 Aug 29;233(4767):975–977. doi: 10.1126/science.3090686. [DOI] [PubMed] [Google Scholar]
  28. Zonana J., Clarke A., Sarfarazi M., Thomas N. S., Roberts K., Marymee K., Harper P. S. X-linked hypohidrotic ectodermal dysplasia: localization within the region Xq11-21.1 by linkage analysis and implications for carrier detection and prenatal diagnosis. Am J Hum Genet. 1988 Jul;43(1):75–85. [PMC free article] [PubMed] [Google Scholar]
  29. Zonana J., Gault J., Davies K. J., Jones M., Browne D., Litt M., Brockdorff N., Rastan S., Clarke A., Thomas N. S. Detection of a molecular deletion at the DXS732 locus in a patient with X-linked hypohidrotic ectodermal dysplasia (EDA), with the identification of a unique junctional fragment. Am J Hum Genet. 1993 Jan;52(1):78–84. [PMC free article] [PubMed] [Google Scholar]
  30. Zonana J. Hypohidrotic (anhidrotic) ectodermal dysplasia: molecular genetic research and its clinical applications. Semin Dermatol. 1993 Sep;12(3):241–246. [PubMed] [Google Scholar]
  31. Zonana J., Jones M., Browne D., Litt M., Kramer P., Becker H. W., Brockdorff N., Rastan S., Davies K. P., Clarke A. High-resolution mapping of the X-linked hypohidrotic ectodermal dysplasia (EDA) locus. Am J Hum Genet. 1992 Nov;51(5):1036–1046. [PMC free article] [PubMed] [Google Scholar]
  32. Zonana J., Roberts S. H., Thomas N. S., Harper P. S. Recognition and reanalysis of a cell line from a manifesting female with X linked hypohidrotic ectodermal dysplasia and an X; autosome balanced translocation. J Med Genet. 1988 Jun;25(6):383–386. doi: 10.1136/jmg.25.6.383. [DOI] [PMC free article] [PubMed] [Google Scholar]

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