Neurocristopathy resembling neurofibromatosis type 1 in an NGF-SV40 transgenic line.
BACKGROUND
Animal models of carcinogenesis have been produced in transgenic mice by directing the expression of oncogenes such as SV40 T antigen and myc to different tissues by creating fusions with promoter/enhancer elements of various mammalian or viral genes.


RESULTS
A transgenic mouse line was created in which SV40 T antigen is under the control of the mouse nerve growth factor (NGF) promoter. While the oncogene is expressed in a wide range of NGF producing tissues, it specifically causes the development of either neurofibromas or neurofibrosarcomas similar to those found in the human disease neurofibromatosis type 1 (NF1). These tumours are completely penetrant and appear after a mean latency of about 8 months. In contrast to the previously reported neurofibromatosis mouse model HTLV-1 tax, the tumours in these transgenic mice arise in Schwann cells rather than perineural fibroblasts and have a very restricted tissue distribution. In a cell line cloned from a neurofibroma from these mice, NGF was detected in the culture medium at levels similar to those produced by cultured primary Schwann cells.


CONCLUSIONS
As all animal model for a heritable neurocristopathy resembling NF1, this mouse should allow study of the pathology and treatment of this disease.
Mazarakis
N D
ND
Norman and Sadie Lee Research Centre, Division of Neurobiology, National Institute for Medical Research, London, UK.
Yannoutsos
N
N
el-Jabbour
J N
JN
Hatton
W
W
Fletcher
R
R
Grosveld
F
F
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D002460:Cell Line; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000235:genetics*; D009456:Neurofibromatosis 1 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012313:RNA / Q000235:genetics / Q000378:metabolism
D000952:Antigens, Polyomavirus Transforming; D009414:Nerve Growth Factors; D012313:RNA