However, genetically engineered mice (GEM) in which mono-allelic germline Nf1 gene loss is coupled with bi-allelic somatic (glial progenitor cell) Nf1 gene inactivation develop brain tumors that do not fully recapitulate the neuropathological features of the human condition.
In this review, we highlight advances in neurofibromatosis type 1 (NF1) genetically engineered mouse brain tumor (glioma) modeling to reveal how cellular and molecular heterogeneity in both the pre-neoplastic/neoplastic and non-neoplastic cellular compartments contribute to gliomagenesis and glioma growth.
We and others have previously shown that brain tumor (glioma) formation in Nf1 genetically engineered mice requires a microenvironment composed of cells heterozygous for a targeted Nf1 mutation.
The close association of neurofibromatosis type 1 (NF1) with gliomas raises the question of whether the NF1 gene may be involved in the pathogenesis of sporadic astrocytic brain tumors.
These findings suggest that neurofibromin and its isoforms have important physiological roles in the human brain and that the altered expression of type I and type II mRNAs in brain tumours may be related to the tumorigenesis.