Sympathetic hyperplasia and neuroblastomas in transgenic mice expressing polyoma middle T antigen

A. Aguzzi, E. F. Wagner, R. L. Williams, Sara Courtneidge

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Transgenic mice carrying a cDNA to the polyoma virus middle T (mT) antigen linked to the thymidine kinase promoter were generated to study the consequences of deregulated expression of mT-associated tyrosine kinase activity in a wide variety of tissues. Four independent transgenic founder animals were obtained, from one of which was established a transgenic line. This mouse and all its offspring developed multiple neuroblastomas between 2 and 3 months of age. Expression of the transgene (assayed by tyrosine kinase assay and in situ hybridization) was restricted to the neurons of the central and peripheral nervous tissue, probably because of a positional effect of the transgene integration. Characteristic preneoplastic lesions in the sympathetic ganglia and in the adrenal medulla were identified from which the neuroblastomas originated. The tumors arising in these mice show striking analogies to human neuroblastomas, including the sites of development of the tumors, their histological and ultrastructural appearance, and the expression of diagnostic markers, such as synaptophysin, and high expression of the N-myc oncogene. This animal model thus provides a unique tool for studying growth control in sympathetic neuroblasts and the pathogenesis of neuroblastoma.

Original languageEnglish (US)
Pages (from-to)533-543
Number of pages11
JournalNew Biologist
Volume2
Issue number6
StatePublished - 1990
Externally publishedYes

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Viral Tumor Antigens
Neuroblastoma
Protein-Tyrosine Kinases
Transgenic Mice
Hyperplasia
Tumors
Animals
Tissue
Synaptophysin
Thymidine Kinase
Transgenes
Viruses
Neurons
Assays
Complementary DNA
Nerve Tissue
Polyomavirus
Sympathetic Ganglia
Genetically Modified Animals
myc Genes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Sympathetic hyperplasia and neuroblastomas in transgenic mice expressing polyoma middle T antigen. / Aguzzi, A.; Wagner, E. F.; Williams, R. L.; Courtneidge, Sara.

In: New Biologist, Vol. 2, No. 6, 1990, p. 533-543.

Research output: Contribution to journalArticle

Aguzzi, A. ; Wagner, E. F. ; Williams, R. L. ; Courtneidge, Sara. / Sympathetic hyperplasia and neuroblastomas in transgenic mice expressing polyoma middle T antigen. In: New Biologist. 1990 ; Vol. 2, No. 6. pp. 533-543.
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