Porcine Model of Huntington\u27s Disease

At present, we are probably the only research facility to be breeding transgenic Huntington\u27s disease minipigs (TgHD). These minipigs express N‐terminal part of human mutated huntingtin including 124Q under the control of human huntingtin promoter. The founder animal, born in 2009, gave birth to four subsequent generations with an equal contribution of wild‐type (WT) and transgenic (TgHD) piglets in all litters. We take different approaches, some of which are unique for large animal models, to study the phenotype development comparing WT and TgHD siblings. In this chapter, we review these approaches and the phenotype progression in the minipigs. Additionally, we outline perspectives in generation of new models using novel methodology and the potential of pig models in preclinical HD studies

Aurora kinase A is essential for meiosis in mouse oocytes.

The Aurora protein kinases are well-established regulators of spindle building and chromosome segregation in mitotic and meiotic cells. In mouse oocytes, there is significant Aurora kinase A (AURKA) compensatory abilities when the other Aurora kinase homologs are deleted. Whether the other homologs, AURKB or AURKC can compensate for loss of AURKA is not known. Using a conditional mouse oocyte knockout model, we demonstrate that this compensation is not reciprocal because female oocyte-specific knockout mice are sterile, and their oocytes fail to complete meiosis I. In determining AURKA-specific functions, we demonstrate that its first meiotic requirement is to activate Polo-like kinase 1 at acentriolar microtubule organizing centers (aMTOCs; meiotic spindle poles). This activation induces fragmentation of the aMTOCs, a step essential for building a bipolar spindle. We also show that AURKA is required for regulating localization of TACC3, another protein required for spindle building. We conclude that AURKA has multiple functions essential to completing MI that are distinct from AURKB and AURKC