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

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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.