Etiology and Pathogenesis > Hereditary Tumor Syndromes

Abstract

Optic Nerve Glioma in Mice Requires Astrocyte Nf1 Gene Inactivation and Nf1 Brain Heterozygosity

M. Livia Bajenaru¹, M. Rosario Hernandez², Arie Perry³, Yuan Zhu⁶, Luis F. Parada⁶, Joel R. Garbow^4,5 and David H. Gutmann¹

¹Departments of Neurology, ²Ophthalmology, ³Pathology, ⁴Radiology, and ⁵Chemistry, Washington University School of Medicine, St. Louis, Missouri, and ⁶Center for Developmental Biology and Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas

Whereas biallelic neurofibromatosis 1 (NF1) inactivation is observed in NF1-associated gliomas, astrocyte-restricted Nf1 conditional knockout mice do not develop gliomas. 
These observations suggest that NF1 glioma formation requires additional cellular or genetic conditions. 
To determine the effect of an Nf1 heterozygous brain environment on NF1 glioma formation, we generated Nf1+/- mice lacking Nf1 expression in astrocytes. 
In contrast to astrocyte-restricted Nf1 conditional knockout mice, Nf1+/- mice lacking Nf1 in astrocytes develop optic nerve gliomas. 
This mouse model demonstrates that Nf1+/- cells contribute to the pathogenesis of gliomas in NF1 and provides a tool for the preclinical evaluation of potential therapeutic interventions for these tumors.

© 2003 American Association for Cancer Research