Deciphering the protective effect of the transient marker gene, Dhcr24, in the adrenal gland inner cortex.

摘要 DHCR24基因首次被发现与阿尔茨海默病的细胞衰老和细胞存活有关。我们 最近发现Dhcr24在小鼠肾上腺内皮质瞬时表达，肾上腺内皮质包括 衰老的肾上腺皮质细胞，在发育过程中经历细胞凋亡。我们还发现，甲状腺激素， 它控制着许多发育过程，如哺乳动物视网膜的分化和细胞凋亡 两栖动物的变态显著上调了肾上腺内皮质中Dhcr24的表达。 有趣的是，这种Dhcr24的上调伴随着衰老的肾上腺皮质细胞凋亡的减少。 在这项提案中，我们的目标是利用我们在肾上腺和下一代测序方面的专业知识 Dhcr24与甲状腺激素介导的抗细胞凋亡关系的研究技术 对衰老的肾上腺皮质细胞的影响。在目标1中，我们将完成Dhcr24的初步表型分析 条件基因敲除小鼠。这将在组织学水平上破译Dhcr24在肾上腺中的作用。在……里面 目的2，我们将比较Dhcr24条件基因敲除小鼠和野生型小鼠肾上腺中的转录 甲状腺激素治疗前后产仔数。这将识别Dhcr24下游基因和 与甲状腺激素介导的抗细胞凋亡效应相关的途径。阐明与疾病相关的基因 Dhcr24将促进我们对Dhcr24介导的抗细胞凋亡作用的理解。甲状腺的鉴定 激素反应基因及其与Dhcr24的联系将有助于理解甲状腺激素和 Dhcr24影响细胞存活和衰老。

Abstract DHCR24 was first identified as a gene associated with cell aging and cell survival in Alzheimer’s disease. We recently found that Dhcr24 is transiently expressed in the mouse adrenal gland inner cortex which consists of aged adrenocortical cells that undergo apoptosis during development. We also found that thyroid hormone, which controls many developmental processes such as differentiation of retina in mammals and apoptosis during metamorphosis in amphibians, significantly upregulates Dhcr24 expression in the adrenal gland inner cortex. Interestingly, this upregulation of Dhcr24 is accompanied by the reduced apoptosis of aged adrenocortical cells. In this proposal, we aim to use our expertise in the adrenal gland and the next generation sequencing technique to study the connection between Dhcr24 and the thyroid hormone-mediated antiapoptotic effect in aged adrenocortical cells. In Aim 1, we will complete the initial phenotypic analysis of the Dhcr24 conditional knockout mice. This will decipher the role of Dhcr24 in the adrenal gland at the histological level. In Aim 2, we will compare transcriptomes in adrenal glands from Dhcr24 conditional knockout mice and wild type littermates before and after thyroid hormone treatment. This will identify Dhcr24 downstream genes and pathways associated with the thyroid hormone-mediated anti-apoptotic effect. Elucidating genes associated with Dhcr24 will advance our understanding of the Dhcr24-mediated anti-apoptotic effect. Identification of the thyroid hormone-responsive genes and their connections with Dhcr24 will help to understand how thyroid hormone and Dhcr24 influence cell survival and aging.