Abnormal brain iron metabolism in Irp2 deficient mice is associated with mild neurological and behavioral impairments.
Abnormal brain iron metabolism in Irp2 deficient mice is associated with mild neurological and behavioral impairments.
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DOI：
10.1371/journal.pone.0098072
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Leibold EA
中科院分区：
文献类型：
--
作者：
Zumbrennen-Bullough KB;Becker L;Garrett L;Hölter SM;Calzada-Wack J;Mossbrugger I;Quintanilla-Fend L;Racz I;Rathkolb B;Klopstock T;Wurst W;Zimmer A;Wolf E;Fuchs H;Gailus-Durner V;de Angelis MH;Romney SJ;Leibold EA
Iron Regulatory Protein 2 (Irp2, Ireb2) is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2−/− mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc), expression are increased and decreased, respectively, in the brain from Irp2−/− mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments.
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影响因子：
29
作者：
Anderson SA;Nizzi CP;Chang YI;Deck KM;Schmidt PJ;Galy B;Damnernsawad A;Broman AT;Kendziorski C;Hentze MW;Fleming MD;Zhang J;Eisenstein RS
通讯作者：
Eisenstein RS
影响因子：
2.5
作者：
Kallnik, Magdalena;Elvert, Ralf;Hoelter, Sabine M.
通讯作者：
Hoelter, Sabine M.
影响因子：
20.3
作者：
Galy, B;Ferring, D;Hentze, MW
通讯作者：
Hentze, MW
影响因子：
6.7
作者：
KONO, SATOSHI;MIYAJIMA, HIROAKI
通讯作者：
MIYAJIMA, HIROAKI
DOI：
10.1073/pnas.0805361105
发表时间：
2008-08-19
影响因子：
11.1
作者：
Ghosh, Manik C.;Tong, Wing-Hang;Rouault, Tracey A.
通讯作者：
Rouault, Tracey A.