Identification and characterization of a novel murine allele of Tmprss6

Haematologica

Volumn 98, Issue 6, 2013, Pages 854-861

  Bartnikas, Thomas B ^a   Steinbicker, Andrea U ^b,c   Campagna, Dean R ^d   Blevins, Sherika ^d   Woodward, Lanette S ^e   Herrera, Carolina ^a   Bloch, Kenneth D ^b   Justice, Monica J ^e   Fleming, Mark D ^d  

^a BROWN UNIVERSITY   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

^c UNIVERSITY OF MÜNSTER   (Germany)

^d BOSTON CHILDREN S HOSPITAL   (United States)

^e BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BONE MORPHOGENETIC PROTEIN 6; HEMOGLOBIN; HEPCIDIN; INHIBITOR OF DIFFERENTIATION 1; IRON; NITROSOUREA DERIVATIVE; SERINE PROTEINASE; TRANSFERRIN;

ALLELE; ANEMIA; ARTICLE; CONTROLLED STUDY; FEMALE; GENE; GENE MUTATION; GENOTYPING TECHNIQUE; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IRON METABOLISM; MALE; MOUSE; MOUSE STRAIN; MUTAGENESIS; NONHUMAN; POLYMERASE CHAIN REACTION; PROTEIN EXPRESSION; QUANTITATIVE TRAIT LOCUS MAPPING; SEQUENCE ALIGNMENT; TMPRSS6 GENE;

ALLELES; AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANIMALS; BONE MORPHOGENETIC PROTEINS; CHROMOSOME MAPPING; ETHYLNITROSOUREA; FEMALE; GENETIC LINKAGE; GENOTYPE; MALE; MEMBRANE PROTEINS; MICE; MICE, KNOCKOUT; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTAGENESIS; MUTATION; PHENOTYPE; PROTEIN CONFORMATION; QUANTITATIVE TRAIT LOCI; SEQUENCE ALIGNMENT; SERINE ENDOPEPTIDASES; SIGNAL TRANSDUCTION;

EID: 84878456393     PISSN: 03906078     EISSN: 15928721     Source Type: Journal    
DOI: 10.3324/haematol.2012.074617     Document Type: Article

References (48)

1. Nguyen N, Judd LM, Kalantzis A, Whittle B, Giraud AS, Van Driel IR. Random mutagenesis of the mouse genome: a strategy for discovering gene function and the molecular basis of disease. Am J Physiol Gastrointest Liver Physiol. 2011;300(1): G1-11.
2. Zhang A-S. Control of systemic iron homeostasis by the hemojuvelin-hepcidin axis. Adv Nutr. 2010;1(1):38-45.
3. Fleming MD. The regulation of hepcidin and its effects on systemic and cellular iron metabolism. Hematology Am Soc Hematol Educ Program. 2008;151-8.
4. Silvestri L, Pagani A, Nai A, De Domenico I, Kaplan J, Camaschella C. The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. Cell Metab. 2008;8(6):502-11.
5. Finberg KE, Heeney MM, Campagna DR, Aydinok Y, Pearson HA, Hartman KR, et al. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat Genet. 2008;40(5):569-71.
6. Guillem F, Lawson S, Kannengiesser C, Westerman M, Beaumont C, Grandchamp B. Two nonsense mutations in the TMPRSS6 gene in a patient with microcytic anemia and iron deficiency. Blood. 2008; 112(5):2089-91.
7. Melis MA, Cau M, Congiu R, Sole G, Barella S, Cao A, et al. A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron. Haematologica. 2008;93(10): 1473-9.
8. Silvestri L, Guillem F, Pagani A, Nai A, Oudin C, Silva M, et al. Molecular mechanisms of the defective hepcidin inhibition in TMPRSS6 mutations associated with ironrefractory iron deficiency anemia. Blood. 2009;113(22):5605-8.
9. Ramsay AJ, Quesada V, Sanchez M, Garabaya C, Sardà MP, Baiget M, et al. Matriptase-2 mutations in iron-refractory iron deficiency anemia patients provide new insights into protease activation mechanisms. Hum Mol Genet. 2009;18 (19):3673-83.
10. Tchou I, Diepold M, Pilotto P-A, Swinkels D, Neerman-Arbez M, Beris P. Haematologic data, iron parameters and molecular findings in two new cases of ironrefractory iron deficiency anaemia. Eur J Haematol. 2009;83(6):595-602.
11. Edison ES, Athiyarath R, Rajasekar T, Westerman M, Srivastava A, Chandy M. A novel splice site mutation c.2278 (-1) G>C in the TMPRSS6 gene causes deletion of the substrate binding site of the serine protease resulting in refractory iron deficiency anaemia. Br J Haematol. 2009;147(5):766-9.
12. De Falco L, Totaro F, Nai A, Pagani A, Girelli D, Silvestri L, et al. Novel TMPRSS6 mutations associated with iron-refractory iron deficiency anemia (IRIDA). Hum Mutat. 2010;31(5):E1390-1405.
13. Altamura S, D'Alessio F, Selle B, Muckenthaler MU. A novel TMPRSS6 mutation that prevents protease auto-activation causes IRIDA. Biochem J. 2010;431 (3):363-71.
14. Choi HS, Yang HR, Song SH, Seo J-Y, Lee KO, Kim H-J. A novel mutation Gly603Arg of TMPRSS6 in a Korean female with ironrefractory iron deficiency anemia. Pediatric Blood & Cancer [Internet]. 2011 May 25 [cited 2011 Sep 8]; Available from: http://www.ncbi.nlm.nih.gov/pubmed/216 18415
15. Sato T, Iyama S, Murase K, Kamihara Y, Ono K, Kikuchi S, et al. Novel missense mutation in the TMPRSS6 gene in a Japanese female with iron-refractory iron deficiency anemia. Int J Hematol. 2011;94 (1):101-3.
16. Guillem F, Kannengiesser C, Oudin C, Lenoir A, Matak P, Donadieu J, et al. Inactive matriptase-2 mutants found in IRIDA patients still repress hepcidin in a transfection assay despite having lost their serine protease activity. Human mutation [Internet]. 2012 May 11 [cited 2012 May 21]; Available from: http://www.ncbi.nlm.nih.gov/pubmed/225 81667
17. Du X, She E, Gelbart T, Truksa J, Lee P, Xia Y, et al. The serine protease TMPRSS6 is required to sense iron deficiency. Science. 2008;320(5879):1088-92.
18. Folgueras AR, De Lara FM, Pendás AM, Garabaya C, Rodríguez F, Astudillo A, et al. Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis. Blood. 2008;112(6):2539-45.
19. Finberg KE, Whittlesey RL, Fleming MD, Andrews NC. Down-regulation of Bmp/Smad signaling by Tmprss6 is required for maintenance of systemic iron homeostasis. Blood. 2010;115(18):3817-26.
20. Kile BT, Hentges KE, Clark AT, Nakamura H, Salinger AP, Liu B, et al. Functional genetic analysis of mouse chromosome 11. Nature. 2003;425(6953):81-6.
21. Tian M, Campagna DR, Woodward LS, Justice MJ, Fleming MD. hem6: an ENUinduced recessive hypochromic microcytic anemia mutation in the mouse. Blood. 2008;112(10):4308-13.
22. Bartnikas TB, Parker CC, Cheng R, Campagna DR, Lim JE, Palmer AA, et al. QTLs for murine red blood cell parameters in LG/J and SM/J F(2) and advanced intercross lines. Mammalian genome: official journal of the International Mammalian Genome Society [Internet]. 2012 Feb 10 [cited 2012 May 21]; Available from: http://www.ncbi.nlm.nih.gov/pubmed/223 22356
23. Meynard D, Vaja V, Sun CC, Corradini E, Chen S, López-Otín C, et al. Regulation of TMPRSS6 by BMP6 and iron in human cells and mice. Blood. 2011;118(3):747-56.
24. Sisay MT, Steinmetzer T, Stirnberg M, Maurer E, Hammami M, Bajorath J, et al. Identification of the first low-molecularweight inhibitors of matriptase-2. J Med Chem. 2010;53(15):5523-35.
25. Bartnikas TB, Andrews NC, Fleming MD. Transferrin is a major determinant of hepcidin expression in hypotransferrinemic mice. Blood. 2011;117(2):630-7.
26. Broman KW, Wu H, Sen S, Churchill GA. R/qtl: QTL mapping in experimental crosses. Bioinformatics. 2003;19(7):889-90.
27. Yu PB, Hong CC, Sachidanandan C, Babitt JL, Deng DY, Hoyng SA, et al. Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol. 2008;4(1):33-41.
28. Yu PB, Deng DY, Lai CS, Hong CC, Cuny GD, Bouxsein ML, et al. BMP type I receptor inhibition reduces heterotopic ossification. Nat Med. 2008;14(12):1363-9.
29. Steinbicker AU, Bartnikas TB, Lohmeyer LK, Leyton P, Mayeur C, Kao SM, et al. Perturbation of hepcidin expression by BMP type I receptor deletion induces iron overload in mice. Blood. 2011;118(15): 4224-30.
30. Pedersen SF, Cala PM. Comparative biology of the ubiquitous Na+/H+ exchanger, NHE1: lessons from erythrocytes. J Exp Zoolog Part A Comp Exp Biol. 2004;301 (7):569-78.
31. Westhoff CM. The structure and function of the Rh antigen complex. Semin Hematol. 2007;44(1):42-50.
32. Tanabe O, Katsuoka F, Campbell AD, Song W, Yamamoto M, Tanimoto K, et al. An embryonic/fetal beta-type globin gene repressor contains a nuclear receptor TR2/TR4 heterodimer. EMBO J. 2002; 21(13):3434-42.
33. Tanabe O, Shen Y, Liu Q, Campbell AD, Kuroha T, Yamamoto M, et al. The TR2 and TR4 orphan nuclear receptors repress Gata1 transcription. Genes Dev. 2007;21(21):2832-44.
34. Broudy VC. Stem cell factor and hematopoiesis. Blood. 1997;90(4):1345-64.
35. Cuny GD, Yu PB, Laha JK, Xing X, Liu J-F, Lai CS, et al. Structure-activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors. Bioorg Med Chem Lett. 2008;18(15):4388-92.
36. Steinbicker AU, Sachidanandan C, Vonner AJ, Yusuf RZ, Deng DY, Lai CS, et al. Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation. Blood. 2011;117(18):4915-23.
37. Krieg L, Milstein O, Krebs P, Xia Y, Beutler B, Du X. Mutation of the gastric hydrogenpotassium ATPase alpha subunit causes iron-deficiency anemia in mice. Blood [Internet]. 2011 Oct 5 [cited 2011 Oct 11]; Available from: http://www.ncbi.nlm.nih.gov/pubmed/219 76678
38. Klebig ML, Wall MD, Potter MD, Rowe EL, Carpenter DA, Rinchik EM. Mutations in the clathrin-assembly gene Picalm are responsible for the hematopoietic and iron metabolism abnormalities in fit1 mice. Proc Natl Acad Sci USA. 2003;100(14):8360-5.
39. Lambe T, Simpson RJ, Dawson S, Bouriez-Jones T, Crockford TL, Lepherd M, et al. Identification of a Steap3 endosomal targeting motif essential for normal iron metabolism. Blood. 2009;113(8):1805-8.
40. Chambers JC, Zhang W, Li Y, Sehmi J, Wass MN, Zabaneh D, et al. Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels. Nat Genet. 2009;41(11):1170-2.
41. Benyamin B, Ferreira MAR, Willemsen G, Gordon S, Middelberg RPS, McEvoy BP, et al. Common variants in TMPRSS6 are associated with iron status and erythrocyte volume. Nat Genet. 2009;41(11):1173-5.
42. Ganesh SK, Zakai NA, Van Rooij FJA, Soranzo N, Smith AV, Nalls MA, et al. Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium. Nat Genet. 2009;41(11):1191-8.
43. Tanaka T, Roy CN, Yao W, Matteini A, Semba RD, Arking D, et al. A genome-wide association analysis of serum iron concentrations. Blood. 2010;115(1):94-6.
44. 1(C) levels via glycemic and nonglycemic pathways. Diabetes. 2010;59(12):3229-39.
45. Kullo IJ, Ding K, Jouni H, Smith CY, Chute CG. A genome-wide association study of red blood cell traits using the electronic medical record. PLoS ONE [Internet]. 2010 [cited 2012 Aug 24];5(9). Available from: http://www.ncbi.nlm.nih.gov/pubmed/209 27387
46. McLaren CE, McLachlan S, Garner CP, Vulpe CD, Gordeuk VR, Eckfeldt JH, et al. Associations between single nucleotide polymorphisms in iron-related genes and iron status in multiethnic populations. PLoS ONE. 2012;7(6):e38339.
47. Béliveau F, Brulé C, Désilets A, Zimmerman B, Laporte SA, Lavoie CL, et al. Essential role of endocytosis of the type II transmembrane serine protease TMPRSS6 in regulating its functionality. J Biol Chem. 2011;286(33): 29035-43.
48. Lenoir A, Deschemin J-C, Kautz L, Ramsay AJ, Roth M-P, Lopez-Otin C, et al. Iron-deficiency anemia from matriptase-2 inactivation is dependent on the presence of functional Bmp6. Blood. 2011;117(2):647-50.