Genetic susceptibility to retinoblastoma in mice

A. E. Griep, D. Lee, J. Krawcek, A. Liem, Daniel Albert, P. F. Lambert

Research output: Contribution to journalArticle

Abstract

Purpose. Inbred strains of laboratory mice exhibit varying susceptibilities to numerous types of cancers. We assessed the genetic susceptibility of certain inbred mouse strains to retinoblastoma induced by the oncogenes from two different DNA tumor viruses, Human papillomavirus type 16 E6 and E7 (HPV-16 E6/E7) and SV40 Large T antigen (SV40 Tag). Methods. Transgenic mice expressing HPV-16 E6/E7 ectopically in the retina and maintained on the FVB inbred genetic background were crossed to two other inbred mouse strains, C57B1/6 and C3H. Transgenic mice expressing SV40 Tag ectopically in the retina and maintained on the C57B1/6 background were crossed onto the FVB background. Mice were scored for retinoblastoma incidence by histological analysis. Simple Sequence Length Polymorphism (SSLP) analysis was used to identify loci contributing to susceptibility. Results. Whereas retinoblastomas arose only infrequently (<5%) when the HPV-16 E6/E7 transgene was carried on the FVB background, tumors arose at 90% penetrance when the transgene was crossed onto the C57B1/6 background. Tumor incidence on the C3H background was intermediate (30%). Retinoblastoma incidence in the SV40 Tag transgenic mice was similarly influenced by the genetic background. Using SSLP analysis, the rd locus was identified as one genetic modulator of susceptibility to retinoblastomas, contributing in part to the low incidence of retinoblastomas in transgenic mice maintained on the FVB background. However, analysis of multiple backcrossed generations of transgenic mice indicates that at least one other independent genetic locus contributes to susceptibility. Experiments are ongoing to identify the additional loci involved in conferring susceptibility to retinoblastoma formation in these transgenic mice. Conclusions. These results demonstrate that genetic susceptibility to retinoblastoma in transgenic mice expressing two different DNA tumor virus oncogenes in the retina is influenced by at least two independent genetic loci.

Original languageEnglish (US)
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996
Externally publishedYes

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Retinoblastoma
Genetic Predisposition to Disease
Transgenic Mice
Human papillomavirus 16
Polyomavirus Transforming Antigens
Inbred Strains Mice
Viral Tumor Antigens
DNA Tumor Viruses
Retina
Genetic Loci
Incidence
Transgenes
Oncogenes
Neoplasms
Penetrance

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Griep, A. E., Lee, D., Krawcek, J., Liem, A., Albert, D., & Lambert, P. F. (1996). Genetic susceptibility to retinoblastoma in mice. Investigative Ophthalmology and Visual Science, 37(3).

Genetic susceptibility to retinoblastoma in mice. / Griep, A. E.; Lee, D.; Krawcek, J.; Liem, A.; Albert, Daniel; Lambert, P. F.

In: Investigative Ophthalmology and Visual Science, Vol. 37, No. 3, 15.02.1996.

Research output: Contribution to journalArticle

Griep, AE, Lee, D, Krawcek, J, Liem, A, Albert, D & Lambert, PF 1996, 'Genetic susceptibility to retinoblastoma in mice', Investigative Ophthalmology and Visual Science, vol. 37, no. 3.
Griep AE, Lee D, Krawcek J, Liem A, Albert D, Lambert PF. Genetic susceptibility to retinoblastoma in mice. Investigative Ophthalmology and Visual Science. 1996 Feb 15;37(3).
Griep, A. E. ; Lee, D. ; Krawcek, J. ; Liem, A. ; Albert, Daniel ; Lambert, P. F. / Genetic susceptibility to retinoblastoma in mice. In: Investigative Ophthalmology and Visual Science. 1996 ; Vol. 37, No. 3.
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abstract = "Purpose. Inbred strains of laboratory mice exhibit varying susceptibilities to numerous types of cancers. We assessed the genetic susceptibility of certain inbred mouse strains to retinoblastoma induced by the oncogenes from two different DNA tumor viruses, Human papillomavirus type 16 E6 and E7 (HPV-16 E6/E7) and SV40 Large T antigen (SV40 Tag). Methods. Transgenic mice expressing HPV-16 E6/E7 ectopically in the retina and maintained on the FVB inbred genetic background were crossed to two other inbred mouse strains, C57B1/6 and C3H. Transgenic mice expressing SV40 Tag ectopically in the retina and maintained on the C57B1/6 background were crossed onto the FVB background. Mice were scored for retinoblastoma incidence by histological analysis. Simple Sequence Length Polymorphism (SSLP) analysis was used to identify loci contributing to susceptibility. Results. Whereas retinoblastomas arose only infrequently (<5{\%}) when the HPV-16 E6/E7 transgene was carried on the FVB background, tumors arose at 90{\%} penetrance when the transgene was crossed onto the C57B1/6 background. Tumor incidence on the C3H background was intermediate (30{\%}). Retinoblastoma incidence in the SV40 Tag transgenic mice was similarly influenced by the genetic background. Using SSLP analysis, the rd locus was identified as one genetic modulator of susceptibility to retinoblastomas, contributing in part to the low incidence of retinoblastomas in transgenic mice maintained on the FVB background. However, analysis of multiple backcrossed generations of transgenic mice indicates that at least one other independent genetic locus contributes to susceptibility. Experiments are ongoing to identify the additional loci involved in conferring susceptibility to retinoblastoma formation in these transgenic mice. Conclusions. These results demonstrate that genetic susceptibility to retinoblastoma in transgenic mice expressing two different DNA tumor virus oncogenes in the retina is influenced by at least two independent genetic loci.",
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