Systemic and cerebral iron homeostasis in ferritin knock-out mice.
Systemic and cerebral iron homeostasis in ferritin knock-out mice.
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DOI：
10.1371/journal.pone.0117435
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Vidal R
中科院分区：
文献类型：
--
作者：
Li W;Garringer HJ;Goodwin CB;Richine B;Acton A;VanDuyn N;Muhoberac BB;Irimia-Dominguez J;Chan RJ;Peacock M;Nass R;Ghetti B;Vidal R
Ferritin, a 24-mer heteropolymer of heavy (H) and light (L) subunits, is the main cellular iron storage protein and plays a pivotal role in iron homeostasis by modulating free iron levels thus reducing radical-mediated damage. The H subunit has ferroxidase activity (converting Fe(II) to Fe(III)), while the L subunit promotes iron nucleation and increases ferritin stability. Previous studies on the H gene (Fth) in mice have shown that complete inactivation of Fth is lethal during embryonic development, without ability to compensate by the L subunit. In humans, homozygous loss of the L gene (FTL) is associated with generalized seizure and atypical restless leg syndrome, while mutations in FTL cause a form of neurodegeneration with brain iron accumulation. Here we generated mice with genetic ablation of the Fth and Ftl genes. As previously reported, homozygous loss of the Fth allele on a wild-type Ftl background was embryonic lethal, whereas knock-out of the Ftl allele (Ftl-/-) led to a significant decrease in the percentage of Ftl-/- newborn mice. Analysis of Ftl-/- mice revealed systemic and brain iron dyshomeostasis, without any noticeable signs of neurodegeneration. Our findings indicate that expression of the H subunit can rescue the loss of the L subunit and that H ferritin homopolymers have the capacity to sequester iron in vivo. We also observed that a single allele expressing the H subunit is not sufficient for survival when both alleles encoding the L subunit are absent, suggesting the need of some degree of complementation between the subunits as well as a dosage effect.
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影响因子：
3.7
作者：
Gkouvatsos K;Fillebeen C;Daba A;Wagner J;Sebastiani G;Pantopoulos K
通讯作者：
Pantopoulos K
影响因子：
4.8
作者：
Ferreira, C;Bucchini, D;Beaumont, C
通讯作者：
Beaumont, C
影响因子：
4.8
作者：
Muhoberac BB;Vidal R
通讯作者：
Vidal R
DOI：
10.1084/jem.20130315
发表时间：
2013-08-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cozzi A;Santambrogio P;Privitera D;Broccoli V;Rotundo LI;Garavaglia B;Benz R;Altamura S;Goede JS;Muckenthaler MU;Levi S
通讯作者：
Levi S
影响因子：
4.7
作者：
Barbeito AG;Garringer HJ;Baraibar MA;Gao X;Arredondo M;Núñez MT;Smith MA;Ghetti B;Vidal R
通讯作者：
Vidal R