Endocrine Abstracts

Introduction: Mutations in AIP have been associated with the familial isolated pituitary adenoma (FIPA) syndrome, an autosomal dominant disease with incomplete penetrance characterised by pituitary adenomas in a familial setting. However, the mechanisms by which AIP inactivation promotes pituitary tumorigenesis are unknown. Studies of AIP in model organisms, such as the fruitfly, harbouring the AIP orthologue CG1847, as well as the zebrafish, are theoretically promising models in discovering possible functions of the AIP gene and understanding pituitary tumorigenesis.

Aim: To establish AIP study models in fruitfly and zebrafish.

Methods: We used RT-PCR and in-situ hybridization (ISH) to study the expression of AIP orthologues in fruitfly and zebrafish, and we have generated transgenic AIP-knockdown fruitfly strains by RNA interference using GAL4/UAS-system.

Results: FlyBase RNA ISH showed that CG1847 gene is expressed in fruitfly from early stages (stage I). We generated several fruitfly crosses, using two different GAL4 drivers (actin and elav, expressed in all cells or all neurons respectively) and two different CG1847 RNAi lines (same RNAi construct on ChrII and ChrIII respectively). When actin-GAL4 flies were crossed with CG1847-R2 RNAi line no viable adult offspring were observed suggesting that complete AIP-knockdown is lethal. When using the nervous system-specific elav-GAL4driver, we were able to confirm CG1847 knockdown in the viable offsprings. Wing-targeted knockdown of AIP resulted in specific wing abnormalities. In zebrafish we were able to prove AIP expression from very early stages of development with a wide-spread expression profile.

Conclusions: We have shown that equivalents of mammalian AIP are present and well conserved in the fruitfly and the zebrafish. We have demonstrated that complete AIP deficiency is lethal in the fruitfly, similar to results in the AIP-KO mice. We suggest that these model organisms are useful to identify AIP protein interactions and to explore possible mechanisms of tumour suppression.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.