The Combined Inactivation of Intestinal and Hepatic ZIP14 Exacerbates Manganese Overload in Mice.
The Combined Inactivation of Intestinal and Hepatic ZIP14 Exacerbates Manganese Overload in Mice.
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DOI：
10.3390/ijms23126495
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发表时间：
2022-06-10
影响因子：
5.6
通讯作者：
Zhao, Ningning
中科院分区：
文献类型：
--
作者：
Fung, Caitlin K.;Zhao, Ningning
ZIP14是新近发现的一种锰转运蛋白，在小肠和肝脏中高水平表达。ZIP14的功能丧失突变可导致全身锰超载，这主要影响中枢神经系统，导致神经疾病。为了阐明肠道ZIP14和肝脏ZIP14在维持全身锰稳态中的作用，我们建立了单组织或双组织Zip14基因敲除小鼠，包括肠道特异性(Zip14-in-KO)、肝脏特异性(Zip14-L-KO)和双(肠和肝脏)Zip14-DKO基因敲除小鼠(Zip14-dko)。以Zip14 FLOX/FLOX小鼠为对照。用电感耦合等离子体质谱(ICPMS)分析比较这些小鼠组织中的锰含量。我们发现，虽然肠道ZIP14的缺失只是适度增加了全身的锰负荷，但肠道和肝脏的ZIP14的缺失都极大地加剧了身体的锰负荷。我们的结果为进一步了解锰代谢提供了新的知识，并为研究ZIP14缺失导致全身锰超载的机制提供了重要的见解。
ZIP14 is a newly identified manganese transporter with high levels of expression in the small intestine and the liver. Loss-of-function mutations in ZIP14 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 Zip14 knockout, including intestine-specific (Zip14-In-KO), liver-specific (Zip14-L-KO), and double (intestine and liver) Zip14-knockout (Zip14-DKO) mice. Zip14flox/flox 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.
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影响因子：
--
作者：
BURNETT, WT;BIGELOW, RR;SHEPPARD, CW
通讯作者：
SHEPPARD, CW
影响因子：
3.8
作者：
Rodan LH;Hauptman M;D'Gama AM;Qualls AE;Cao S;Tuschl K;Al-Jasmi F;Hertecant J;Hayflick SJ;Wessling-Resnick M;Yang ET;Berry GT;Gropman A;Woolf AD;Agrawal PB
通讯作者：
Agrawal PB
DOI：
10.1016/0021-9681(66)90094-4
发表时间：
1966-01-01
期刊：
JOURNAL OF CHRONIC DISEASES
影响因子：
--
作者：
SCHROEDER, HA;BALASSA, JJ;TIPTON, IH
通讯作者：
TIPTON, IH
影响因子：
3.5
作者：
Juneja, Monica;Shamim, Uzma;Faruq, Mohammed
通讯作者：
Faruq, Mohammed
影响因子：
3.8
作者：
Dorman, DC;Struve, MF;Wong, BA
通讯作者：
Wong, BA