Detection of spontaneous schwannomas by MRI in a transgenic murine model of neurofibromatosis type 2

S. M. Messerli, Y. Tang, M. Giovannini, R. Bronson, R. Weissleder, X. O. Breakefield

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Abstract

Spontaneous schwannomas were detected by magnetic resonance imaging (MRI) in a transgenic murine model of neurofibromatosis type 2 (NF2) expressing a dominant mutant form of merlin under the Schwann cell-specific PO promoter. Approximately 85% of the investigated mice showed putative tumors by 24 months of age. Specifically, 21% of the mice showed tumors in the intercostal muscles, 14% in the limb muscles, 7% in the spinal cord and spinal ganglia, 7% in the external ear, 14% in the muscle of the abdominal region, and 7% in the intestine; 66% of the female mice had uterine tumors. Multiple tumors were detected by MRI in 21% of mice. The tumors were isointense with muscle by T1-weighted MRI, showed strong enhancement following administration of gadolinium-DTPA, and were markedly hyperintense by T2-weighted MRI, all hallmarks of the clinical manifestation. Hematoxylin and eosin staining and immunohistochemistry indicated that the tumors consisted of schwannomas and Schwann cell hyperplasias. The lesions stained positively for S-100 protein and a marker antigen for the mutated transgenic NF2 protein, confirming that the imaged tumors and areas of hyperplasia were of Schwann cell origin and expressed the mutated NF2 protein. Tumors were highly infectable with a recombinant herpes simplex virus type 1 vector, hrR3, which contains the reporter gene, lacZ. The ability to develop schwannoma growth with a noninvasive imaging technique will allow assessment of therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)501-509
Number of pages9
JournalNeoplasia
Volume4
Issue number6
DOIs
Publication statusPublished - Jan 1 2002

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Keywords

  • Herpes simplex virus
  • Magnetic resonance imaging
  • Neurofibromatosis
  • Transgenic mice
  • Tumor

ASJC Scopus subject areas

  • Cancer Research

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