For example, more complex mouse models employing the Cre-Lox system to generate a bi-allelic loss of NF1 in a specific cell lineage (e.g., Schwann cell) often require mutations in other tumor suppressor genes (such as TP53 or INK4a/ARF that are frequently mutated in NF1-associated tumors) to successfully generate neurofibromas (17, 18), albeit with major limitations. This evidence concerns the gene NF1 and plexiform neurofibroma.