title: Optic nerve glioma in mice requires astrocyte Nf1 gene inactivation and Nf1 brain heterozygosity.
abstract: 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.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: M Livia
authors.initials: ML
authors.lastname: Bajenaru
authors.forename: M Rosario
authors.initials: MR
authors.lastname: Hernandez
authors.forename: Arie
authors.initials: A
authors.lastname: Perry
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Luis F
authors.initials: LF
authors.lastname: Parada
authors.forename: Joel R
authors.initials: JR
authors.lastname: Garbow
authors.forename: David H
authors.initials: DH
authors.lastname: Gutmann
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016514:Genes, Neurofibromatosis 1 / Q000502:physiology*; D006579:Heterozygote; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009456:Neurofibromatosis 1 / Q000150:complications / Q000235:genetics* / Q000473:pathology; D020339:Optic Nerve Glioma / Q000235:genetics* / Q000473:pathology