Mouse Models of HRS-NF2 Interaction
Annual rept. 1 Jan-31 Dec 2005
CEDARS-SINAI MEDICAL CENTER LOS ANGELES CA
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Neurofibromatosis 2 NF2 is a tumor suppressor gene syndrome characterized by the development of tumors of Schwann cell, meningeal, and ependymal origin. NF2 is also the gene most commonly mutated in sporadic tumors of these cell types. With previous support from the NF2 program of the Army Medical Branch we have identified hepatocyte growth factor regulated kinase substrate HRS as a protein that interacts with schwannomin. Studies by us and others have indicated a role for HRS in growth factor receptor trafficking and downregulation of signaling, but also established a role for HRS in cytokine and IGF1- mediated signaling to the STAT pathway. In the first year of funding, we have continued our in vitro studies of Hrs partial proteins and have initiated mouse studies to test interactions. We have identified several different Hrs molecules that show dominant negative effects. Our initial intercrosses of Hrs- mice with Nf2- mice have been successful. However, we have noticed slightly reduced litter size and some evidence for segregation distortion. This may influence our overall timetable in that it may be more costly and lengthy to produce the number of animals necessary for analysis.
- Medicine and Medical Research