Tanycytes and Nonthyroidal Illness

Tanycytes 和非甲状腺疾病

• 批准号: 7649705
• 负责人: RONALD Michael LECHAN
• 金额: $ 27.68万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-10 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7649705
• 关键词: Animals; Cell Culture System; Cell Culture Techniques; Cell Line; Cell Nucleus; Cells; Development; Endotoxins; Enzymes; Ependymal Cell; Fasting; Floor; Fluorescence-Activated Cell Sorting; Genes; Homeostasis; Hypothalamic structure; Hypothyroidism; Immune; Individual; Infection; Iodothyronine Deiodinase; Microarray Analysis; Mus; Neurons; Neurosecretory Systems; Physiological; Pituitary Gland; Production; Regulation; Role; Structure of nucleus infundibularis hypothalami; Syndrome; Third ventricle structure; Thyroid Gland; Thyroid Hormones; Time; Tissues; Transgenic Mice; Triiodothyronine; base; density; diphtheria toxin receptor; falls; feeding; laser capture microdissection; median eminence; mouse model; pituitary thyroid axis; prohormone; public health relevance; pyroglutamyl-peptidase II; recombinase; selective expression; tissue culture

DESCRIPTION (provided by applicant): Tanycytes are specialized ependymal cells found in high density along the floor and ventrolateral walls of the third ventricle between the rostral and caudal limits of the hypothalamic median eminence. Little is known about these cells but their expression of type 2 iodothyronine deiodinase (D2), an enzyme critical for conversion of thyroid hormone into its active form, and responsiveness to fasting and endotoxin in several animal species, has raised the possibility that tanycytes are involved in energy homeostasis and contribute to the mechanism by which circulating thyroid hormone levels fall in individuals with severe infection, termed the "nonthyroidal illness syndrome". To facilitate understanding of the importance of tanycytes in neuroendocrine regulation through effects on the hypothalamic-pituitary-thyroid (HPT) axis and feeding-related centers in the arcuate nucleus, we propose to identify tanycytes-specific genes using laser capture microdissection and microarray analysis and develop transgenic mice that express Cre recombinase specifically in tanycytes. These mice will be used to develop a tanycyte cell culture system, and to specifically ablate alpha and/or beta n vivo by developing double transgenic mice after crossing with a Cre-inducible diphtheria toxin receptor mouse line. These studies are expected to generate new information about the biologic importance of tanycytes and their role in neuroendocrine regulation of the HPT axis and in energy homeostasis. PUBLIC HEALTH RELEVANCE: Tanycytes are specialized cells that line the floor and ventrolateral walls of the third ventricle. Compelling evidence suggests they have an important role in generating thyroid hormone due to high expression of type 2 iodothyronine deiodinase, an enzyme critical for conversion of the prohormone, T4, into the biologically active thyroid hormone, T3. We have proposed, therefore, that tanycytes are involved in regulation of the hypothalamic-pituitary-thyroid (HPT) axis and energy homeostasis. To facilitate the study of these cells in neuroendocrine regulation, we will identify tanycyte specific genes by laser capture microdissection and microarray analysis to develop transgenic mice that express Cre recombinase specifically in tanycytes. These mice will be used to develop double transgenic mice in which tanycytes are selectively ablated or marked with GFP to allow isolation by fluorescence-activated cell sorting (FACS) for tissue culture.

描述（由申请人提供）：tanycytes是沿着下丘脑中位数隆起的尾部和尾部限制之间的第三个心室的高密度和腹侧壁的高密度和腹侧壁。对这些细胞知之甚少，但是它们对2型碘甲醇脱硫酶（D2）的表达是一种对将甲状腺激素转化为其活性形式的至关重要的酶，并且对几种动物的禁食和内毒素的反应性提高了tomycys在能量稳定性中涉及促成的机构的趋势，并提高了thonycyts的可能性。 “非甲状腺疾病综合征”。通过对下丘脑 - 垂体 - 甲状腺（HPT）轴（HPT）轴和与喂养相关的中心的影响，我们建议使用激光特异性基因鉴定自动排位式分析和微型捕获分析，从tanycytes。这些小鼠将用于开发一种丹氏菌细胞培养系统，并通过与CRE诱导的白喉毒素受体小鼠系进行杂交后，通过开发双转基因小鼠来具体消融α和/或βn n vivo。预计这些研究将产生有关tanycytes的生物学重要性及其在HPT轴和能量稳态中的神经内分泌调节中的作用的新信息。公共卫生相关性：tanycytes是在第三个心室的地板和腹外侧壁上排列的专门细胞。令人信服的证据表明，由于2型碘甲醇脱碘酶的高表达，它们在产生甲状腺激素方面具有重要作用，这种酶是蛋白激素T4转化为生物活性甲状腺激素T3的酶。因此，我们提出，tanycytes参与了下丘脑 - 垂体 - 甲状腺（HPT）轴和能量稳态的调节。为了促进对神经内分泌调节中这些细胞的研究，我们将通过激光捕获微分辨率和微阵列分析来鉴定tanycyte特异性基因，从而开发出特有在tanycytes中表达CRE重组酶的转基因小鼠。这些小鼠将用于开发双转基因小鼠，其中tanycytes被选择性地消融或用GFP标记，以通过荧光激活的细胞分选（FACS）分离以进行组织培养。