Brain tumours and lymphomas in transgenic mice that carry HTLV-I LTR/c-myc and Ig/tax genes

N. Benvenisty, D. M. Ornitz, G. L. Bennett, B. G. Sahagan, A. Kuo, Robert Cardiff, P. Leder

Research output: Contribution to journalArticle

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Abstract

The human T-cell leukemia virus type 1 (HTLV-I) is associated with adult CD4+ T-cell leukemia (ATL) and tropical spastic paraparesis (TSP). In as much as only a small percentage of individuals infected with HTLV-I develop either disease, we set out to model a genetic partner for this virus in an effort to understand and possibly reproduce its pathophysiology. To this end we have developed a binary set of transgenic mice, one bearing the relatively inactive HTLV-I long terminal repeat (LTR) positioned to drive the c-myc oncogene and another bearing a fusion transgene consisting of the immunoglobulin promoter/enhancer driving the gene for the HTLV-I transcription activator, tax. Alone, the tax construct, though expressed in the thymus, spleen, lung and brain, has no deleterious effect. Alone, the HTLV-I LTR/c-myc construct is expressed at very low levels in lymphoid cells and occasionally induces lymphomas in older animals. When these two transgenic lines are mated, bigenic offspring harboring both transgenes exhibit dramatic tumor formation. As in the human, these animals develop CD4+ T-cell lymphomas, but they also develop central nervous system tumors by 25-90 days of age. The syndrome, which is 100% penetrant and lethal, provides an animal model for adult T-cell lymphoma and a source of cultured cells of neurogenic origin.

Original languageEnglish (US)
Pages (from-to)2399-2405
Number of pages7
JournalOncogene
Volume7
Issue number12
StatePublished - Jan 1 1992
Externally publishedYes

Fingerprint

pX Genes
Deltaretrovirus
Immunoglobulin Genes
Terminal Repeat Sequences
Brain Neoplasms
Transgenic Mice
Lymphoma
T-Cell Lymphoma
Transgenes
Tropical Spastic Paraparesis
Central Nervous System Neoplasms
Adult T Cell Leukemia Lymphoma
myc Genes
Genetic Models
Thymus Gland
Immunoglobulins
Cultured Cells
Spleen
Animal Models
Lymphocytes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Benvenisty, N., Ornitz, D. M., Bennett, G. L., Sahagan, B. G., Kuo, A., Cardiff, R., & Leder, P. (1992). Brain tumours and lymphomas in transgenic mice that carry HTLV-I LTR/c-myc and Ig/tax genes. Oncogene, 7(12), 2399-2405.

Brain tumours and lymphomas in transgenic mice that carry HTLV-I LTR/c-myc and Ig/tax genes. / Benvenisty, N.; Ornitz, D. M.; Bennett, G. L.; Sahagan, B. G.; Kuo, A.; Cardiff, Robert; Leder, P.

In: Oncogene, Vol. 7, No. 12, 01.01.1992, p. 2399-2405.

Research output: Contribution to journalArticle

Benvenisty, N, Ornitz, DM, Bennett, GL, Sahagan, BG, Kuo, A, Cardiff, R & Leder, P 1992, 'Brain tumours and lymphomas in transgenic mice that carry HTLV-I LTR/c-myc and Ig/tax genes', Oncogene, vol. 7, no. 12, pp. 2399-2405.
Benvenisty N, Ornitz DM, Bennett GL, Sahagan BG, Kuo A, Cardiff R et al. Brain tumours and lymphomas in transgenic mice that carry HTLV-I LTR/c-myc and Ig/tax genes. Oncogene. 1992 Jan 1;7(12):2399-2405.
Benvenisty, N. ; Ornitz, D. M. ; Bennett, G. L. ; Sahagan, B. G. ; Kuo, A. ; Cardiff, Robert ; Leder, P. / Brain tumours and lymphomas in transgenic mice that carry HTLV-I LTR/c-myc and Ig/tax genes. In: Oncogene. 1992 ; Vol. 7, No. 12. pp. 2399-2405.
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