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Generation of a Mouse Model for Schwannomatosis

Principal Investigator: CHANG, LONG-SHENG
Institution Receiving Award: RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL
Program: NFRP
Proposal Number: NF080021
Award Number: W81XWH-09-1-0094
Funding Mechanism: Exploration-Hypothesis Development Award
Partnering Awards:
Award Amount: $144,000.00


PUBLIC ABSTRACT

Schwannomatosis is a genetic disorder that causes multiple tumors called schwannomas to grow on cranial, spinal, and peripheral nerves. In addition, people with schwannomatosis have problems with chronic pain that often exceeds their neurological problems. Unfortunately, at the current time there is no blood test to determine if a patient has schwannomatosis, and there is no drug for the treatment of schwannomatosis-associated tumors. Thus, generation of an animal model for schwannomatosis is of urgent need, particularly in light of recent identification of mutations in two tumor suppressor genes named INI1/SNF5 and NF2 in multiple schwannomas from patients with schwannomatosis.

The goal of this study is to generate a mouse model for schwannomatosis by simultaneously inactivating both the mouse Ini1/Snf5 and Nf2 genes in specifically affected tissues including Schwann cells. To achieve this goal, we have designed a conditional gene knockout approach using the regulatory sequence of the NF2 gene to achieve target gene inactivation. We will also use the noninvasive small-animal magnetic resonance imaging (MRI) to monitor any tumor formation in these genetically engineered mice. If successful, this mouse model will allow us to study how simultaneous inactivation of both the INI1/SNF5 and NF2 tumor suppressor genes leads to the development of schwannomatosis. In addition, it will represent the first animal model that will aid in preclinical drug testing, ultimately leading to a cure of this horrible and painful disease.