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Science 10 December 1999:
Vol. 286. no. 5447, pp. 2172 - 2176
DOI: 10.1126/science.286.5447.2172
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Reports

Mouse Models of Tumor Development in Neurofibromatosis Type 1 

Karen Cichowski, 1* T. Shane Shih, 12* Earlene Schmitt, 13 Sabrina Santiago, 1 Karlyne Reilly, 1 Margaret E. McLaughlin, 4 Roderick T. Bronson, 5 Tyler Jacks 16dagger

Neurofibromatosis type 1 (NF1) is a prevalent familial cancer syndrome resulting from germ line mutations in the NF1 tumor suppressor gene. Hallmark features of the disease are the development of benign peripheral nerve sheath tumors (neurofibromas), which can progress to malignancy. Unlike humans, mice that are heterozygous for a mutation in Nf1 do not develop neurofibromas. However, as described here, chimeric mice composed in part of Nf1-/- cells do, which demonstrates that loss of the wild-type Nf1 allele is rate-limiting in tumor formation. In addition, mice that carry linked germ line mutations in Nf1 and p53 develop malignant peripheral nerve sheath tumors (MPNSTs), which supports a cooperative and causal role for p53 mutations in MPNST development. These two mouse models provide the means to address fundamental aspects of disease development and to test therapeutic strategies.

1 Department of Biology and Center for Cancer Research and
6 Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2 Merck & Co., Whitehouse Station, NJ 08889, USA.
3 Breast Center, Baylor College of Medicine, One Baylor Plaza, MS 600, Houston, TX 77030, USA.
4 Brigham and Women's Hospital, Department of Pathology, Boston, MA 02115, USA.
5 Department of Pathology, Tufts University Schools of Medicine and Veterinary Medicine, Boston, MA 02111, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: tjacks{at}mit.edu

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