Background
Neurofibromatosis type 2 (NF2) is an autosomal dominant tumor predisposition syndrome resulting from mutations in the NF2 gene. NF2 patients are prone to developing schwannomas, which are benign tumors originating from Schwann cells of the peripheral nervous system. Though the hallmark of NF2 is the development of bilateral vestibular schwannomas, schwannomas can occur on any cranial or peripheral nerve. Facial nerve schwannoma (FNS) is the most common primary neoplasm of the facial nerve, although it is uncommon overall. Due to the rarity of FNS, animal models are imperative for therapeutic testing of pharmaceutical compounds. The Postn-Cre;Nf2flox/flox mouse model is known to develop cranial nerve schwannomas, including FNS. However, the nature of these tumors has not been robustly characterized.

Methods
Postn-Cre;Nf2flox/flox and control littermates were euthanized at 12 months of age. A novel method was employed for dissection of the intratemporal facial nerve. Whole heads or isolated facial nerves were formalin-fixed and paraffin embedded. Sections were stained by hematoxylin and eosin or immunohistochemistry. Schwann cell density and tumorlets were quantified in geniculate ganglia and peri-geniculate facial nerves. Comparative statistical analysis was performed using Student’s t-test (GraphPad Prism).

Results
In this study, we report the first thorough histopathological analysis of FNS development in the Postn-Cre;Nf2flox/flox mouse model. Schwann cell density is increased in mutant facial nerves and geniculate ganglia compared to control (p<0.001). Tumorlets are present only in Postn- Cre;Nf2flox/flox mutant mouse ganglia (p<0.01). Neuron density is decreased in mutant geniculate ganglia (p<0.001). Merlin, S100, SOX10, GFAP, FABP7, Neurofilament, and Ki-67 immunostaining confirmed a Schwann cell phenotype.

Conclusion
The Postn-Cre;Nf2flox/flox mouse model demonstrates consistent and predictable development of facial nerve schwannoma. While this model has been described to develop cranial nerve schwannomas, our study establishes the first quantifiable readout of tumor burden through measurement of Schwann cell and tumorlet density. These findings provide a novel endpoint for preclinical testing of targeted therapies for neurofibromatosis type 2-associated cranial nerve schwannomas in the Postn-Cre;Nf2flox/flox mouse model.

Facial Nerve Schwannoma Development in a Genetically Engineered Neurofibromatosis Type 2Mouse Model

Basic Science | Otolaryngology - Head and Neck Surgery

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Facial Nerve Schwannoma Development in a Genetically Engineered Neurofibromatosis Type 2Mouse Model

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