Thf, role of over expression of n-myc in retinoblastoma development in transgenic mice

Daniel Albert, C. L. Wilkerson, J. M. Iokken, J. J. Windle

Research output: Contribution to journalArticle

Abstract

Introduction :The development of retinoblastoma results from the inactivation of both copies of Ihe Rb tumor suppressor gene. However, it remains unclear whether additional genetic alterations are required for retinoblastoma formation. One candidate gene is N-myc, which has been shown to be overexpressed, and in some cases amplified, in human retinoblastomas. Purpose: We examined whether N-myc overexpression and Rb inactivation cooperate in the development of retinoblastoma in a transgenic mouse model. Methods: Transgenic mice expressing an IRBP-Nmyc transgene were interbred to IRBP-E7 mice to generate mice of the following genotypes: N-myc+/E7+ (n=12),N-myc+/E7- (n=16), N-myc-/E7+(n=15). Mice were sacrificed between 3 and 7 months of age. The eyes were enucleated and examined histologically by a masked observer. Results: IRBP-E7 mice develop photoreceplor apoptosis due to pRb inactivation, and for reasons that are presently unclear, develop late RPE tumors and dysplasia. However, none of the mice developed retinoblastoma. Conclusion: N-myc over expression does not appear to cooperate with Rb loss for retinoblastoma development in this model. The elevated N-myc expression seen in retinoblastomas may reflect its normal level of expression in embryonic retinoblasts.

Original languageEnglish (US)
JournalInvestigative Ophthalmology and Visual Science
Volume38
Issue number4
StatePublished - Dec 1 1997
Externally publishedYes

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Retinoblastoma
Transgenic Mice
myc Genes
Tumor Suppressor Genes
Transgenes
Genotype
Apoptosis
Neoplasms

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Thf, role of over expression of n-myc in retinoblastoma development in transgenic mice. / Albert, Daniel; Wilkerson, C. L.; Iokken, J. M.; Windle, J. J.

In: Investigative Ophthalmology and Visual Science, Vol. 38, No. 4, 01.12.1997.

Research output: Contribution to journalArticle

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abstract = "Introduction :The development of retinoblastoma results from the inactivation of both copies of Ihe Rb tumor suppressor gene. However, it remains unclear whether additional genetic alterations are required for retinoblastoma formation. One candidate gene is N-myc, which has been shown to be overexpressed, and in some cases amplified, in human retinoblastomas. Purpose: We examined whether N-myc overexpression and Rb inactivation cooperate in the development of retinoblastoma in a transgenic mouse model. Methods: Transgenic mice expressing an IRBP-Nmyc transgene were interbred to IRBP-E7 mice to generate mice of the following genotypes: N-myc+/E7+ (n=12),N-myc+/E7- (n=16), N-myc-/E7+(n=15). Mice were sacrificed between 3 and 7 months of age. The eyes were enucleated and examined histologically by a masked observer. Results: IRBP-E7 mice develop photoreceplor apoptosis due to pRb inactivation, and for reasons that are presently unclear, develop late RPE tumors and dysplasia. However, none of the mice developed retinoblastoma. Conclusion: N-myc over expression does not appear to cooperate with Rb loss for retinoblastoma development in this model. The elevated N-myc expression seen in retinoblastomas may reflect its normal level of expression in embryonic retinoblasts.",
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AU - Wilkerson, C. L.

AU - Iokken, J. M.

AU - Windle, J. J.

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AB - Introduction :The development of retinoblastoma results from the inactivation of both copies of Ihe Rb tumor suppressor gene. However, it remains unclear whether additional genetic alterations are required for retinoblastoma formation. One candidate gene is N-myc, which has been shown to be overexpressed, and in some cases amplified, in human retinoblastomas. Purpose: We examined whether N-myc overexpression and Rb inactivation cooperate in the development of retinoblastoma in a transgenic mouse model. Methods: Transgenic mice expressing an IRBP-Nmyc transgene were interbred to IRBP-E7 mice to generate mice of the following genotypes: N-myc+/E7+ (n=12),N-myc+/E7- (n=16), N-myc-/E7+(n=15). Mice were sacrificed between 3 and 7 months of age. The eyes were enucleated and examined histologically by a masked observer. Results: IRBP-E7 mice develop photoreceplor apoptosis due to pRb inactivation, and for reasons that are presently unclear, develop late RPE tumors and dysplasia. However, none of the mice developed retinoblastoma. Conclusion: N-myc over expression does not appear to cooperate with Rb loss for retinoblastoma development in this model. The elevated N-myc expression seen in retinoblastomas may reflect its normal level of expression in embryonic retinoblasts.

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