Generation And Use Of Merlin-Deficient Human Schwann Cells For A High-Throughput Chemical Genomics Screening Assay

Keywords

Drug discovery; High-throughput viability assay; Human Schwann cell line; Merlin; Neurofibromatosis type 2 (NF2); Schwannoma

Abstract

Schwannomas are benign nerve tumors that occur sporadically in the general population and in those with neurofibromatosis type 2 (NF2), a tumor predisposition genetic disorder. NF2-associated schwannomas and most sporadic schwannomas are caused by inactivating mutations in Schwann cells in the neurofibromatosis type 2 gene (NF2) that encodes the merlin tumor suppressor. Despite their benign nature, schwannomas and especially vestibular schwannomas cause considerable morbidity. The primary available therapies are surgery or radiosurgery which usually lead to loss of function of the compromised nerve. Thus, there is a need for effective chemotherapies. We established an untransformed merlin-deficient human Schwann cell line for use in drug discovery studies for NF2-associated schwannomas. We describe the generation of human Schwann cells (HSCs) with depletion of merlin and their application in high-throughput screening of chemical libraries to identify compounds that decrease their viability. This NF2-HSC model is amenable for use in independent labs and high-throughput screening (HTS) facilities.

Publication Date

1-1-2018

Publication Title

Methods in Molecular Biology

Volume

1739

Number of Pages

161-173

Document Type

Article; Book Chapter

Personal Identifier

scopus

DOI Link

https://doi.org/10.1007/978-1-4939-7649-2_11

Socpus ID

85044189905 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/85044189905

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