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Ovarian phenotype of IKKβ conditional knockout mouse
Summary
These studies are investigating the importance of NFκβ signalling to ovarian function by deleting IKKβ mice from the ovarian granulosa cells of mice. The initial analysis of the phenotype suggests an interesting but subtle phenotype.
Description
NFκβ signalling appears to play a role in tumours of granulosa cells but it also has a role in normal folliculogenesis. This is a pathway that has not been fully examined or understood. It is generally regarded as being pro-proliferative and anti-apoptotic.
In order to identify its function in normal granulosa cells, our strategy has been to delete one of the critical signalling genes in the pathway IKKβ mice which are null for IKKβ, have been bred and are currently being analysed.
The study will involve histological analysis of the ovaries from the knockout mice as well as exploring their response to stimuli and also the granulosa cells will be expanded and characterised in vitro.
This will provide a powerful tool for not only understanding the functional role of NFκβ signalling in the ovary but also for identifying the genes targeted by NFκβ for regulation.
We are also interested to explore the consequences for oestrogen receptor β (ERβ) signalling given the role NFκB appears to have in inhibiting ERβ signalling.
Funding
National Health and Medical Research Council
Ovarian Cancer Research Foundation
Selected Publications
Chu, S., Alexiadis, M. and Fuller, P.J. (2009) Proteasome Inhibition by bortezomib decreases proliferation and increases apoptosis in ovarian granulosa cell tumors. Reproductive Sciences 16:397-407.
Jamieson, S., and Fuller, P.J. (2008) Management of granulosa cell tumour of the ovary Current Opinion in Oncology 20: 560-564.
Chu, S. Nishi, Y., Yanase, T., Nawata, H. and Fuller, P.J. (2004) Transrepression of estrogen receptor β signaling by nuclear factor-κB in ovarian granulosa cells. Molecular Endocrinology 18: 1919-1928.