Genetic analysis of hypothalamic tanycyte function

描述（由申请人提供）：下丘脑伸长细胞是一种寻找明确功能的细胞类型，已有近60年的历史。伸长细胞在中基底下丘脑中的突出存在，是广泛的食欲和情绪行为的关键中央调节器，导致了对其生理功能的许多猜测。已经积累了大量的间接证据，表明它们参与了从控制血脑屏障的渗透性，到调节神经激素的释放和控制摄食，到成人神经发生的过程。然而，到目前为止，还不可能在体内有效地和有选择性地操纵伸长细胞的功能，到目前为止，这些提出的伸长细胞的功能还没有被直接测试。我们已经确定了一组在下丘脑伸长细胞中选择性表达的基因。我们建议使用这些数据来产生转基因小鼠系，这些小鼠系将允许选择性和有条件地消融tanycytes，并允许在tanycytes中选择性和可诱导的基于cre的重组。然后，我们将使用这些细胞系选择性地切除下丘脑伸长细胞，并检查这些细胞对下丘脑生理学方面的贡献。

DESCRIPTION (provided by applicant): Hypothalamic tanycytes have been a cell type in search of a defined function for nearly sixty years. The prominent presence of tanycytes in the mediobasal hypothalamus, the key central regulator for a broad range of appetitive and emotional behaviors, has led to much speculation about their physiological function. A great deal of mostly indirect evidence has been accumulated to suggest their involvement in processes ranging from control of blood-brain barrier permeability, to regulation of neurohormone release and control of feeding, to adult neurogenesis. However, it has so far not been possible to effectively and selectively manipulate the function of tanycytes in vivo, and thus far these proposed functions of tanycytes have not been directed tested. We have identified a set of genes that are selectively expressed in hypothalamic tanycytes. We propose to use this data to generate transgenic mouse lines that will permit both selective and conditional ablation of tanycytes and selective and inducible Cre-based recombination in tanycytes. We will then selectively ablate hypothalamic tanycytes using these lines, and examine the contribution of these cells to aspects of hypothalamic physiology. PUBLIC HEALTH RELEVANCE: Hypothalamic tanycytes have been proposed to regulate many different physiological processes. However, it has thus far not been possible to effectively and selectively manipulate tanycyte function, and thus these proposed functions of tanycytes have not been directly tested. We propose to generate transgenic mice that will allow us to conditionally and selectively manipulate gene expression in hypothalamic tanycytes. We will use these lines to selectively ablate hypothalamic tanycytes and to study the behavior and physiology of mice lacking these cells.