Abnormal brain iron metabolism in Irp2 deficient mice is associated with mild neurological and behavioral impairments

PLoS ONE

Volumn 9, Issue 6, 2014, Pages

  Zumbrennen Bullough, Kimberly B ^a   Becker, Lore ^b   Garrett, Lillian ^b   Hölter, Sabine M ^b   Calzada Wack, Julia ^b   Mossbrugger, Ilona ^b   Quintanilla Fend, Leticia ^b   Racz, Ildiko ^b,c   Rathkolb, Birgit ^b,d   Klopstock, Thomas ^e,i,j   Wurst, Wolfgang ^b,f,h,i,j   Zimmer, Andreas ^c   Wolf, Eckhard ^d   Fuchs, Helmut ^b   Gailus Durner, Valerie ^b   Hrabě De Angelis, Martin ^b,f,g   Romney, Steven J ^k   Leibold, Elizabeth A ^k  

^a HARVARD MEDICAL SCHOOL   (United States)

^b INSTITUTE OF EPIDEMIOLOGY   (Germany)

^c UNIVERSITY OF BONN   (Germany)

^d UNIVERSITY OF MUNICH   (Germany)

^e LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^f TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^g GERMAN CENTER FOR DIABETES RESEARCH DZD   (Germany)

^h MAX PLANCK INSTITUTE OF PSYCHIATRY   (Germany)

ⁱ GERMAN CENTER FOR NEURODEGENERATIVE DISEASES DZNE   (Germany)

^j German Center for Diabetes Research ^*  (Germany)

^k UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CD71 ANTIGEN; FERRITIN; IRON REGULATORY PROTEIN 2; IRON; TFRC PROTEIN, MOUSE; TRANSFERRIN RECEPTOR;

AGING; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BEHAVIOR DISORDER; CONTROLLED STUDY; DISEASE ASSOCIATION; IRON METABOLISM; IRON METABOLISM DISORDER; LOCOMOTION; MALE; MILD COGNITIVE IMPAIRMENT; MOTOR COORDINATION; MOUSE; NERVE FIBER DEGENERATION; NEURODEGENERATION WITH BRAIN IRON ACCUMULATION; NOCICEPTION; NONHUMAN; OLIGODENDROGLIA; PHENOTYPE; PROTEIN CONTENT; PROTEIN DEFICIENCY; PROTEIN EXPRESSION; PROTEIN FUNCTION; WHITE MATTER; ANIMAL; ANIMAL BEHAVIOR; BRAIN; EXPLORATORY BEHAVIOR; GENETICS; KNOCKOUT MOUSE; METABOLISM; MOTOR ACTIVITY; NERVE CELL; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY;

ANIMALS; BEHAVIOR, ANIMAL; BRAIN; EXPLORATORY BEHAVIOR; IRON; IRON REGULATORY PROTEIN 2; MICE; MICE, KNOCKOUT; MOTOR ACTIVITY; NEURONS; NOCICEPTION; OLIGODENDROGLIA; RECEPTORS, TRANSFERRIN; WHITE MATTER;

EID: 84902438197     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0098072     Document Type: Article

References (48)

1. Ganz T, Nemeth E (2012) Hepcidin and iron homeostasis. Biochim Biophys Acta 1823: 1434-1443.
2. Simcox JA, McClain DA (2013) Iron and diabetes risk. Cell Metab 17: 329-341.
3. Rouault TA (2013) Iron metabolism in the CNS: implications for neurodegenerative diseases. Nat Rev Neurosci.
4. Rao R, Georgieff MK (2007) Iron in fetal and neonatal nutrition. Semin Fetal Neonatal Med 12: 54-63.
5. Lozoff B, Georgieff MK (2006) Iron deficiency and brain development. Semin Pediatr Neurol 13: 158-165.
6. Youdim MB (2008) Brain iron deficiency and excess; cognitive impairment and neurodegeneration with involvement of striatum and hippocampus. Neurotox Res 14: 45-56.
7. Fretham SJ, Carlson ES, Wobken J, Tran PV, Petryk A, et al. (2012) Temporal manipulation of transferrin-receptor-1-dependent iron uptake identifies a sensitive period in mouse hippocampal neurodevelopment. Hippocampus 22: 1691-1702.
8. Dusek P, Jankovic J, Le W (2012) Iron dysregulation in movement disorders. Neurobiol Dis 46: 1-18.
9. Burn J, Chinnery PF (2006) Neuroferritinopathy. Semin Pediatr Neurol 13: 176-181.
10. Kono S, Miyajima H (2006) Molecular and pathological basis of aceruloplasminemia. Biol Res 39: 15-23.
11. Hentze MW, Muckenthaler MU, Galy B, Camaschella C (2010) Two to tango: regulation of Mammalian iron metabolism. Cell 142: 24-38.
12. Anderson CP, Shen M, Eisenstein RS, Leibold EA (2012) Mammalian iron metabolism and its control by iron regulatory proteins. Biochim Biophys Acta 1823: 1468-1483.
13. Vashisht AA, Zumbrennen KB, Huang X, Powers DN, Durazo A, et al. (2009) Control of iron homeostasis by an iron-regulated ubiquitin ligase. Science 326: 718-721.
14. Salahudeen AA, Thompson JW, Ruiz JC, Ma HW, Kinch LN, et al. (2009) An E3 ligase possessing an iron-responsive hemerythrin domain is a regulator of iron homeostasis. Science 326: 722-726.
15. Moroishi T, Nishiyama M, Takeda Y, Iwai K, Nakayama KI (2011) The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo. Cell Metab 14: 339-351.
16. Sanchez M, Galy B, Schwanhaeusser B, Blake J, Bahr-Ivacevic T, et al. (2011) Iron regulatory protein-1 and -2: transcriptome-wide definition of binding mRNAs and shaping of the cellular proteome by iron regulatory proteins. Blood 118: e168-179.
17. LaVaute T, Smith S, Cooperman S, Iwai K, Land W, et al. (2001) Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat Genet 27: 209-214.
18. Meyron-Holtz EG, Ghosh MC, Iwai K, LaVaute T, Brazzolotto X, et al. (2004) Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis. EMBO J 23: 386-395.
19. Galy B, Ferring D, Hentze MW (2005) Generation of conditional alleles of the murine iron regulatory protein (Irp)-1 and -2 genes. Genesis 43: 181-188.
20. Anderson SA, Nizzi CP, Chang YI, Deck KM, Schmidt PJ, et al. (2013) The IRP1-HIF-2alpha axis coordinates iron and oxygen sensing with erythropoiesis and iron absorption. Cell Metab 17: 282-290.
21. Ghosh MC, Zhang DL, Jeong SY, Kovtunovych G, Ollivierre-Wilson H, et al. (2013) Deletion of iron regulatory protein 1 causes polycythemia and pulmonary hypertension in mice through translational derepression of HIF2alpha. Cell Metab 17: 271-281.
22. Wilkinson N, Pantopoulos K (2013) IRP1 regulates erythropoiesis and systemic iron homeostasis by controlling HIF2alpha mRNA translation. Blood 122: 1658-1668.
23. Cooperman SS, Meyron-Holtz EG, Olivierre-Wilson H, Ghosh MC, McConnell JP, et al. (2005) Microcytic anemia, erythropoietic protoporphyria, and neurodegeneration in mice with targeted deletion of iron-regulatory protein 2. Blood 106: 1084-1091.
24. Galy B, Ferring D, Minana B, Bell O, Janser HG, et al. (2005) Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2). Blood 106: 2580-2589.
25. Smith SR, Cooperman S, Lavaute T, Tresser N, Ghosh M, et al. (2004) Severity of neurodegeneration correlates with compromise of iron metabolism in mice with iron regulatory protein deficiencies. Ann N Y Acad Sci 1012: 65-83.
26. Galy B, Holter SM, Klopstock T, Ferring D, Becker L, et al. (2006) Iron homeostasis in the brain: complete iron regulatory protein 2 deficiency without symptomatic neurodegeneration in the mouse. Nat Genet 38: 967-969; discussion 969-970.
27. Guo B, Yu Y, Leibold EA (1994) Iron regulates cytoplasmic levels of a novel iron-responsive element-binding protein without aconitase activity. J Biol Chem 269: 24252-24260.
28. Yu Y, Radisky E, Leibold EA (1992) The iron-responsive element binding protein. Purification, cloning, and regulation in rat liver. J Biol Chem 267: 19005-19010.
29. Leibold EA, Munro HN (1988) Cytoplasmic protein binds in vitro to a highly conserved sequence in the 59 untranslated region of ferritin heavy- and light-subunit mRNAs. Proc Natl Acad Sci U S A 85: 2171-2175.
30. Phillips JD, Bergonia HA, Reilly CA, Franklin MR, Kushner JP (2007) A porphomethene inhibitor of uroporphyrinogen decarboxylase causes porphyria cutanea tarda. Proc Natl Acad Sci U S A 104: 5079-5084.
31. Ohl F, Holsboer F, Landgraf R (2001) The modified hole board as a differential screen for behavior in rodents. Behav Res Methods Instrum Comput 33: 392-397.
32. Kallnik M, Elvert R, Ehrhardt N, Kissling D, Mahabir E, et al. (2007) Impact of IVC housing on emotionality and fear learning in male C3HeB/FeJ and C57BL/6J mice. Mamm Genome 18: 173-186.
33. Neff F, Flores-Dominguez D, Ryan DP, Horsch M, Schroder S, et al. (2013) Rapamycin extends murine lifespan but has limited effects on aging. J Clin Invest 123: 3272-3291.
34. Mogil JS (1999) The genetic mediation of individual differences in sensitivity to pain and its inhibition. Proc Natl Acad Sci U S A 96: 7744-7751.
35. Ghosh MC, Tong WH, Zhang D, Ollivierre-Wilson H, Singh A, et al. (2008) Tempol-mediated activation of latent iron regulatory protein activity prevents symptoms of neurodegenerative disease in IRP2 knockout mice. Proc Natl Acad Sci U S A 105: 12028-12033.
36. Grabill C, Silva AC, Smith SS, Koretsky AP, Rouault TA (2003) MRI detection of ferritin iron overload and associated neuronal pathology in iron regulatory protein-2 knockout mice. Brain Res 971: 95-106.
37. Todorich B, Pasquini JM, Garcia CI, Paez PM, Connor JR (2009) Oligodendrocytes and myelination: the role of iron. Glia 57: 467-478.
38. Dickinson TK, Connor JR (1998) Immunohistochemical analysis of the transferrin receptor: regional and cellular distribution in the hypotransferrinemic (hpx) mouse brain. Brain Research 801: 171-181.
39. Leitner DF, Connor JR (2012) Functional roles of transferrin in the brain. Biochim Biophys Acta 1820: 393-402.
40. Gerlai R (1996) Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype? Trends Neurosci 19: 177-181.
41. Watase K, Zoghbi HY (2003) Modelling brain diseases in mice: the challenges of design and analysis. Nat Rev Genet 4: 296-307.
42. Yoshiki A, Moriwaki K (2006) Mouse phenome research: implications of genetic background. Ilar J 47: 94-102.
43. Pham CT, MacIvor DM, Hug BA, Heusel JW, Ley TJ (1996) Long-range disruption of gene expression by a selectable marker cassette. Proc Natl Acad Sci U S A 93: 13090-13095.
44. Crusio WE (2004) Flanking gene and genetic background problems in genetically manipulated mice. Biol Psychiatry 56: 381-385.
45. Leboeuf RC, Tolson D, Heinecke JW (1995) Dissociation between tissue iron concentrations and transferrin saturation among inbred mouse strains. J Lab Clin Med 126: 128-136.
46. Connor JR, Menzies SL (1996) Relationship of iron to oligodendrocytes and myelination. Glia 17: 83-93.
47. Jeong SY, Crooks DR, Wilson-Ollivierre H, Ghosh MC, Sougrat R, et al. (2011) Iron insufficiency compromises motor neurons and their mitochondrial function in Irp2-null mice. PLoS One 6: e25404.
48. Bunting M, Bernstein KE, Greer JM, Capecchi MR, Thomas KR (1999) Targeting genes for self-excision in the germ line. Genes Dev 13: 1524-1528.