514. THE REPRODUCTIVE PHENOTYPE OF THE IKKβ CONDITIONAL KNOCKOUT MOUSE

Abstract

Nuclear factor-κB (NF-κB) designates a family of transcription factors that have been shown to modulate antiviral, inflammatory and immune responses. Activation of NF-κB is dependent on IKKβ a component of the IκB kinase (IKK) complex which promotes degradation of IκB inhibitory proteins and allows nuclear translocation of NF-κB. Our studies in ovarian granulosa cell tumour cell lines (COV434 and KGN) indicate that NF-κB signalling is constitutively activated. FSH has been reported to increase XIAP expression through NFκB activity in granulosa cells, but beyond that the role of NFκB signalling in folliculogenesis has not been elucidated. To establish the significance of NF-κB signalling in the ovary (and testis), we have generated a gonadal specific IKKbeta conditional knockout mouse. A transgenic mouse line containing floxed IKKβ alleles (gift of M Karin, UCSD) was crossed with a cre mouse line (gift of M Matzuk, BCM) expressing the recombinase in anti-Müllerian hormone receptor expressing cells (granulosa cells or Sertoli cells). The resulting mice will not express IKKβ in granulosa cells or Sertoli cells and thus cannot activate the classical NFκB signalling pathway. On histological assessment, the ovaries and testes from flox x cre (heterogenous) mice appear normal with follicles of all developmental stages and corpora lutea. Preliminary data suggests that breeding with the heterogenous females resulted in increased litter sizes. The histology of the testes is also unremarkable. The mice homozygous for the deletion of IKKβ in the granulosa cells appear healthy and a preliminary assessment does not reveal gross morphological abnormalities of the ovaries. The results of detailed histological and overall assessment of these mice will be presented. These IKK conditional knockout mice should provide insights into the role of NFκB signalling in gonadal function.