Characterizing Tumor-Induced Ataxia in a Vestibular Schwannoma Mouse Model.

Abstract

NF2-related schwannomatosis (NF2-SWN) is an autosomal dominant tumor predisposition syndrome caused by germline mutations in the NF2 tumor suppressor gene. The disease is characterized by the development of bilateral vestibular schwannomas (VSs), which progressively enlarge and result in hearing loss, imbalance, and ataxia-symptoms that profoundly affect patients' quality of life. No FDA-approved pharmacologic treatments are currently available. Among the neurological deficits, ataxia remains a particularly debilitating yet understudied manifestation, largely due to the lack of robust preclinical models for its evaluation. In this study, we developed a set of behavioral assays to systematically assess tumor-induced ataxia in an orthotopic mouse model of VS-associated hearing loss and ataxia. These tests allow quantitative measurement of balance and motor coordination deficits arising from tumor burden. This experimental platform enables mechanistic studies of tumor-induced cerebellar dysfunction and provides a valuable tool for preclinical evaluation of therapeutic strategies. By integrating behavioral assessments with tumor biology and hearing tests, this approach facilitates the characterization of both tumor-suppressive and neuroprotective treatment effects. Ultimately, these assays offer a versatile framework that can also be applied to other neurological disorders characterized by ataxia, expanding their utility beyond NF2-SWN.