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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Dec 1;89(23):11421–11425. doi: 10.1073/pnas.89.23.11421

Malignancy of eye melanomas originating in the retinal pigment epithelium of transgenic mice after genetic ablation of choroidal melanocytes.

B Mintz 1, A J Klein-Szanto 1
PMCID: PMC50562  PMID: 1454829

Abstract

Eye tumors of the retinal pigment epithelium (RPE) have been thought generally to be benign, whereas choroidal ones are malignant. To test this assumption in mice, the W/Wv (Kit) mutant genotype was introduced into melanoma-prone transgenic mice whose recombinant simian virus 40 transforming sequences are specifically expressed in pigment cells. W/Wv causes programmed death of neural crest-derived pigment cells, including choroidal ones, but leaves intact the brain-derived pigment cells, such as those in the RPE. Dysplastic cells arose in the RPE, contiguous with frank melanotic neoplasms. Invasion of the optic nerve, and tumor growth outside the orbit, attested to the malignancy of these RPE-derived melanomas. The widespread melanosis previously seen in mice with this transgene was absent when W/Wv was added, thus validating its chief origin from neural crest cells.

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Selected References

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  1. Albert D. M., Rabson A. S., Dalton A. J. In vitro neoplastic transformation of uveal and retinal tissue by oncogenic DNA viruses. Invest Ophthalmol. 1968 Aug;7(4):357–365. [PubMed] [Google Scholar]
  2. Bodenstein L., Sidman R. L. Growth and development of the mouse retinal pigment epithelium. I. Cell and tissue morphometrics and topography of mitotic activity. Dev Biol. 1987 May;121(1):192–204. doi: 10.1016/0012-1606(87)90152-7. [DOI] [PubMed] [Google Scholar]
  3. Bradl M., Klein-Szanto A., Porter S., Mintz B. Malignant melanoma in transgenic mice. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):164–168. doi: 10.1073/pnas.88.1.164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Capel B., Mintz B. Neonatal W-mutant mice are favorable hosts for tracking development of marked hematopoietic stem cells. Exp Hematol. 1989 Sep;17(8):872–876. [PubMed] [Google Scholar]
  5. Chang C. W., Roque R. S., Defoe D. M., Caldwell R. B. An improved method for isolation and culture of pigment epithelial cells from rat retina. Curr Eye Res. 1991 Nov;10(11):1081–1086. doi: 10.3109/02713689109020348. [DOI] [PubMed] [Google Scholar]
  6. Deol M. S. The relationship between abnormalities of pigmentation and of the inner ear. Proc R Soc Lond B Biol Sci. 1970 Apr 7;175(1039):201–217. doi: 10.1098/rspb.1970.0019. [DOI] [PubMed] [Google Scholar]
  7. Dutt K., Scott M., Del Monte M., Agarwal N., Sternberg P., Srivastava S. K., Srinivasan A. Establishment of human retinal pigment epithelial cell lines by oncogenes. Oncogene. 1990 Feb;5(2):195–200. [PubMed] [Google Scholar]
  8. Klein-Szanto A., Bradl M., Porter S., Mintz B. Melanosis and associated tumors in transgenic mice. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):169–173. doi: 10.1073/pnas.88.1.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. MINTZ B., RUSSELL E. S. Gene-induced embryological modifications of primordial germ cells in the mouse. J Exp Zool. 1957 Mar;134(2):207–237. doi: 10.1002/jez.1401340202. [DOI] [PubMed] [Google Scholar]
  10. MIYAMOTO M., FITZPATRICK T. B. On the nature of the pigment in retinal pigment epithelium. Science. 1957 Sep 6;126(3271):449–450. doi: 10.1126/science.126.3271.449. [DOI] [PubMed] [Google Scholar]
  11. Markert C L, Silvers W K. The Effects of Genotype and Cell Environment on Melanoblast Differentiation in the House Mouse. Genetics. 1956 May;41(3):429–450. doi: 10.1093/genetics/41.3.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mintz B. Clonal basis of mammalian differentiation. Symp Soc Exp Biol. 1971;25:345–370. [PubMed] [Google Scholar]
  13. Mintz B., Fleischman R. A. Teratocarcinomas and other neoplasms as developmental defects in gene expression. Adv Cancer Res. 1981;34:211–278. doi: 10.1016/s0065-230x(08)60243-2. [DOI] [PubMed] [Google Scholar]
  14. NICHOLS S. E., Jr, REAMS W. M., Jr The occurrence and morphogenesis of melanocytes in the connective tissues of the PET/MCV mouse strain. J Embryol Exp Morphol. 1960 Mar;8:24–32. [PubMed] [Google Scholar]
  15. Nakhleh R. E., Wick M. R., Rocamora A., Swanson P. E., Dehner L. P. Morphologic diversity in malignant melanomas. Am J Clin Pathol. 1990 Jun;93(6):731–740. doi: 10.1093/ajcp/93.6.731. [DOI] [PubMed] [Google Scholar]
  16. Nocka K., Majumder S., Chabot B., Ray P., Cervone M., Bernstein A., Besmer P. Expression of c-kit gene products in known cellular targets of W mutations in normal and W mutant mice--evidence for an impaired c-kit kinase in mutant mice. Genes Dev. 1989 Jun;3(6):816–826. doi: 10.1101/gad.3.6.816. [DOI] [PubMed] [Google Scholar]
  17. Nocka K., Tan J. C., Chiu E., Chu T. Y., Ray P., Traktman P., Besmer P. Molecular bases of dominant negative and loss of function mutations at the murine c-kit/white spotting locus: W37, Wv, W41 and W. EMBO J. 1990 Jun;9(6):1805–1813. doi: 10.1002/j.1460-2075.1990.tb08305.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ts'o M. O., Friedman E. The retinal pigment epithelium. 3. Growth and development. Arch Ophthalmol. 1968 Aug;80(2):214–216. doi: 10.1001/archopht.1968.00980050216012. [DOI] [PubMed] [Google Scholar]
  19. Tso M. O., Albert D. M. Pathological condition of the retinal pigment epithelium. Neoplasms and nodular non-neoplastic lesions. Arch Ophthalmol. 1972 Jul;88(1):27–38. doi: 10.1001/archopht.1972.01000030029007. [DOI] [PubMed] [Google Scholar]

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