School of Nutritional Sciences and Wellness, The University of Arizona, Tucson, AZ 85721, USA.
Int J Mol Sci. 2022 Jun 10;23(12):6495. doi: 10.3390/ijms23126495.
ZIP14 is a newly identified manganese transporter with high levels of expression in the small intestine and the liver. Loss-of-function mutations in can lead to systemic manganese overload, which primarily affects the central nervous system, causing neurological disorders. To elucidate the roles of intestinal ZIP14 and hepatic ZIP14 in maintaining systemic manganese homeostasis, we generated mice with single-tissue or two-tissue knockout, including intestine-specific (-In-KO), liver-specific (-L-KO), and double (intestine and liver) -knockout (-DKO) mice. mice were used as the control. Tissue manganese contents in these mice were compared using inductively coupled plasma mass spectrometry (ICP-MS) analysis. We discovered that although the deletion of intestinal ZIP14 only moderately increased systemic manganese loading, the deletion of both intestinal and hepatic ZIP14 greatly exacerbated the body's manganese burden. Our results provide new knowledge to further the understanding of manganese metabolism, and offer important insights into the mechanisms underlying systemic manganese overload caused by the loss of ZIP14.
ZIP14 是一种新发现的锰转运蛋白，在小肠和肝脏中表达水平较高。 编码 ZIP14 的基因突变会导致全身性锰过载，主要影响中枢神经系统，引起神经紊乱。为了阐明肠道 ZIP14 和肝脏 ZIP14 在维持系统锰稳态中的作用，我们生成了组织特异性敲除 ZIP14 的小鼠，包括肠道特异性敲除（-In-KO）、肝脏特异性敲除（-L-KO）和双组织（肠道和肝脏）敲除（-DKO）小鼠。 野生型小鼠作为对照。通过电感耦合等离子体质谱（ICP-MS）分析比较这些小鼠组织中的锰含量。我们发现，尽管肠道 ZIP14 的缺失仅适度增加了系统锰负荷，但肠道和肝脏 ZIP14 的缺失大大加剧了机体的锰负担。我们的研究结果为进一步了解锰代谢提供了新知识，并为 ZIP14 缺失引起的系统性锰过载的机制提供了重要的见解。
