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Volumn 24, Issue 5, 2004, Pages 2063-2073

Null Mutation of the Lmo4 Gene or a Combined Null Mutation of the Lmo1/ Lmo3 Genes Causes Perinatal Lethality, and Lmo4 Controls Neural Tube Development in Mice

Author keywords

[No Author keywords available]

Indexed keywords

GENE PRODUCT; LIM PROTEIN; LMO1 PROTEIN; LMO2 PROTEIN; LMO4 PROTEIN; UNCLASSIFIED DRUG;

EID: 10744229888     PISSN: 02707306     EISSN: None     Source Type: Journal    
DOI: 10.1128/MCB.24.5.2063-2073.2004     Document Type: Article
Times cited : (73)

References (56)
  • 1
    • 0023551350 scopus 로고
    • Cloning and expression of the mouse pgk-1 gene and the nucleotide sequence of its promoter
    • Adra, C. N., P. H. Boer, and M. W. McNurney. 1987. Cloning and expression of the mouse pgk-1 gene and the nucleotide sequence of its promoter. Gene 60:65-74.
    • (1987) Gene , vol.60 , pp. 65-74
    • Adra, C.N.1    Boer, P.H.2    McNurney, M.W.3
  • 2
    • 0023953685 scopus 로고
    • The mechanism of chromosomal translocation t(11;14) involving the T-cell receptor Cδ locus on human chromosome 14q11 and a transcribed region of chromosome 11p15
    • Boehm, T., R. Baer, I. Lavenir, A. Forster, J. J. Waters, E. Nacheva, and T. H. Babbitts. 1988. The mechanism of chromosomal translocation t(11;14) involving the T-cell receptor Cδ locus on human chromosome 14q11 and a transcribed region of chromosome 11p15. EMBO J. 7:385-394.
    • (1988) EMBO J. , vol.7 , pp. 385-394
    • Boehm, T.1    Baer, R.2    Lavenir, I.3    Forster, A.4    Waters, J.J.5    Nacheva, E.6    Babbitts, T.H.7
  • 3
    • 0025759278 scopus 로고
    • The rhombotin family of cysteine-rich LIM-domain oncogenes: Distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13
    • Boehm, T., L. Foroni, Y. Kaneko, M. P. Perutz, and T. H. Babbitts. 1991. The rhombotin family of cysteine-rich LIM-domain oncogenes: distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13. Proc. Natl. Acad. Sci. USA 88:4367-4371.
    • (1991) Proc. Natl. Acad. Sci. USA , vol.88 , pp. 4367-4371
    • Boehm, T.1    Foroni, L.2    Kaneko, Y.3    Perutz, M.P.4    Babbitts, T.H.5
  • 4
    • 0025311015 scopus 로고
    • The rhombotin gene belongs to a class of transcriptional regulators with a potential novel protein dimerisation motif
    • Boehm, T., L. Foroni, M. Kennedy, and T. H. Rabbitts. 1990. The rhombotin gene belongs to a class of transcriptional regulators with a potential novel protein dimerisation motif. Oncogene 5:1103-1105.
    • (1990) Oncogene , vol.5 , pp. 1103-1105
    • Boehm, T.1    Foroni, L.2    Kennedy, M.3    Rabbitts, T.H.4
  • 5
    • 0025873097 scopus 로고
    • Developmentally regulated and tissue-specific expression of mRNAs encoding the two alternative forms of the LIM domain oncogene rhombotin: Evidence for thymus expression
    • Boehm, T., M.-G. Spillantini, M. V. Sofroniew, M. A. Surani, and T. H. Rabbitts. 1991. Developmentally regulated and tissue-specific expression of mRNAs encoding the two alternative forms of the LIM domain oncogene rhombotin: evidence for thymus expression. Oncogene 6:695-703.
    • (1991) Oncogene , vol.6 , pp. 695-703
    • Boehm, T.1    Spillantini, M.-G.2    Sofroniew, M.V.3    Surani, M.A.4    Rabbitts, T.H.5
  • 6
    • 0036849901 scopus 로고    scopus 로고
    • Differential expression of a transcription regulatory factor, the LIM domain only 4 protein Lmo4, in muscle sensory neurons
    • Chen, H. H., J. W. Yip, A. F. Stewart, and E. Frank. 2002. Differential expression of a transcription regulatory factor, the LIM domain only 4 protein Lmo4, in muscle sensory neurons. Development 129:4879-4889.
    • (2002) Development , vol.129 , pp. 4879-4889
    • Chen, H.H.1    Yip, J.W.2    Stewart, A.F.3    Frank, E.4
  • 8
    • 0025925068 scopus 로고
    • 2H), a mutation affecting development of mouse neural tube, shows a deletion within the paired homeodomain of Pax-3
    • 2H), a mutation affecting development of mouse neural tube, shows a deletion within the paired homeodomain of Pax-3. Cell 67:767-774.
    • (1991) Cell , vol.67 , pp. 767-774
    • Epstein, D.J.1    Vekemans, M.2    Gros, P.3
  • 9
    • 0020793569 scopus 로고
    • A technique for radiolabelling DNA restriction endonuclease fragments to high specific activity
    • Feinberg, A. P., and B. A. Vogelstein. 1983. A technique for radiolabelling DNA restriction endonuclease fragments to high specific activity. Anal. Biochem. 132:6-13.
    • (1983) Anal. Biochem. , vol.132 , pp. 6-13
    • Feinberg, A.P.1    Vogelstein, B.A.2
  • 11
    • 0025328511 scopus 로고
    • Novel cysteine-rich motif and homeodomain in the product of the Caenorhabditis elegans cell lineage gene lin-11
    • Freyd, G., S. K. Kim, and H. R. Horvitz. 1990. Novel cysteine-rich motif and homeodomain in the product of the Caenorhabditis elegans cell lineage gene lin-11. Nature 344:876-879.
    • (1990) Nature , vol.344 , pp. 876-879
    • Freyd, G.1    Kim, S.K.2    Horvitz, H.R.3
  • 13
    • 0032541488 scopus 로고    scopus 로고
    • The oncogenic T cell LIM-protein Lmo2 forms part of a DNA-binding complex specifically in immature T cells
    • Grutz, G., K. Bucher, I. Lavenir, R. Larson, T. Larson, and T. H. Rabbitts. 1998. The oncogenic T cell LIM-protein Lmo2 forms part of a DNA-binding complex specifically in immature T cells. EMBO J. 17:4594-4605.
    • (1998) EMBO J. , vol.17 , pp. 4594-4605
    • Grutz, G.1    Bucher, K.2    Lavenir, I.3    Larson, R.4    Larson, T.5    Rabbitts, T.H.6
  • 14
    • 0032569833 scopus 로고    scopus 로고
    • Identification of the LMO4 gene encoding an interaction partner of the LIM-binding protein LDB1/NLI1: A candidate for displacement by LMO proteins in T cell acute leukaemia
    • Grutz, G., A. Forster, and T. H. Rabbitts. 1998. Identification of the LMO4 gene encoding an interaction partner of the LIM-binding protein LDB1/NLI1: a candidate for displacement by LMO proteins in T cell acute leukaemia. Oncogene 17:2799-2803.
    • (1998) Oncogene , vol.17 , pp. 2799-2803
    • Grutz, G.1    Forster, A.2    Rabbitts, T.H.3
  • 15
    • 0033503556 scopus 로고    scopus 로고
    • Mini-review: Toward understanding mechanisms of genetic neural tube defects in mice
    • Harris, M. J., and D. M. Juriloff. 1999. Mini-review: toward understanding mechanisms of genetic neural tube defects in mice. Teratology 60:292-305.
    • (1999) Teratology , vol.60 , pp. 292-305
    • Harris, M.J.1    Juriloff, D.M.2
  • 16
    • 0033155798 scopus 로고    scopus 로고
    • Expression of LMO-4 in the central nervous system of the embryonic and adult mouse
    • Hermanson, O., T. M. Sugihara, and B. Andersen. 1999. Expression of LMO-4 in the central nervous system of the embryonic and adult mouse. Cell. Mol. Biol. (Noisy-Le-Grand) 45:677-686.
    • (1999) Cell. Mol. Biol. (Noisy-Le-Grand) , vol.45 , pp. 677-686
    • Hermanson, O.1    Sugihara, T.M.2    Andersen, B.3
  • 17
    • 16944364278 scopus 로고    scopus 로고
    • Expression of LIM protein genes Lmo1, Lmo2, and Lmo3 in adult mouse hippocampus and other forebrain regions: Differential regulation by seizure activity
    • Hinks, G. L., B. Shah, S. J. French, L. S. Campos, K. Staley, J. Hughes, and M. V. Sofroniew. 1997. Expression of LIM protein genes Lmo1, Lmo2, and Lmo3 in adult mouse hippocampus and other forebrain regions: differential regulation by seizure activity. J. Neurosci. 17:5549-5559.
    • (1997) J. Neurosci. , vol.17 , pp. 5549-5559
    • Hinks, G.L.1    Shah, B.2    French, S.J.3    Campos, L.S.4    Staley, K.5    Hughes, J.6    Sofroniew, M.V.7
  • 19
    • 0029848478 scopus 로고    scopus 로고
    • Characterization of a cerebellar granule cell-specific gene encoding the gamma-aminobutyric acid type A receptor alpha 6 subunit
    • Jones, A., S. Bahn, A. L. Grant, M. Kohler, and W. Wisden. 1996. Characterization of a cerebellar granule cell-specific gene encoding the gamma-aminobutyric acid type A receptor alpha 6 subunit. J. Neurochem. 67:907-916.
    • (1996) J. Neurochem. , vol.67 , pp. 907-916
    • Jones, A.1    Bahn, S.2    Grant, A.L.3    Kohler, M.4    Wisden, W.5
  • 20
    • 0025280050 scopus 로고
    • Insulin gene enhancer binding protein Isl-1 is a member of a novel class of proteins containing both a homeo- and a cys-his domain
    • Karlsson, O., S. Thor, T. Norberg, H. Ohlsson, and T. Edlund. 1990. Insulin gene enhancer binding protein Isl-1 is a member of a novel class of proteins containing both a homeo- and a cys-his domain. Nature 344:879-882.
    • (1990) Nature , vol.344 , pp. 879-882
    • Karlsson, O.1    Thor, S.2    Norberg, T.3    Ohlsson, H.4    Edlund, T.5
  • 21
    • 0021101221 scopus 로고
    • Analysis of a bacterial hygromycin B resistance gene by transcriptional and translational fusions and by DNA sequencing
    • Kaster, K. R., S. G. Burgett, R. N. Rao, and T. D. Ingolia. 1983. Analysis of a bacterial hygromycin B resistance gene by transcriptional and translational fusions and by DNA sequencing. Nucleic Acids Res. 11:6895-6911.
    • (1983) Nucleic Acids Res. , vol.11 , pp. 6895-6911
    • Kaster, K.R.1    Burgett, S.G.2    Rao, R.N.3    Ingolia, T.D.4
  • 22
    • 0032530133 scopus 로고    scopus 로고
    • Identification and characterization of LMO4, an LMO gene with a novel pattern of expression during embryogenesis
    • Kenny, D. A., L. W. Jurata, Y. Saga, and G. N. Gill. 1998. Identification and characterization of LMO4, an LMO gene with a novel pattern of expression during embryogenesis. Proc. Natl. Acad. Sci. USA 95:11257-11262.
    • (1998) Proc. Natl. Acad. Sci. USA , vol.95 , pp. 11257-11262
    • Kenny, D.A.1    Jurata, L.W.2    Saga, Y.3    Gill, G.N.4
  • 23
    • 0022448678 scopus 로고
    • Diversity and rearrangement of the human T cell rearranging γ genes: Nine germ-line variable genes belonging to two subgroups
    • LeFranc, M.-P., A. Forster, R. Baer, M. A. Stinson, and T. H. Rabbitts. 1986. Diversity and rearrangement of the human T cell rearranging γ genes: nine germ-line variable genes belonging to two subgroups. Cell 45:237-246.
    • (1986) Cell , vol.45 , pp. 237-246
    • LeFranc, M.-P.1    Forster, A.2    Baer, R.3    Stinson, M.A.4    Rabbitts, T.H.5
  • 24
    • 0024564420 scopus 로고
    • The t(11;14)(p15;q11) in a T-cell acute lymphoblastic leukemia cell line activates multiple transcripts, including Ttg-1, a gene encoding a potential zinc finger protein
    • McGuire, E. A., R. D. Hockett, K. M. Pollock, M. F. Bartholdi, S. J. O'Brien, and S. J. Korsmeyer. 1989. The t(11;14)(p15;q11) in a T-cell acute lymphoblastic leukemia cell line activates multiple transcripts, including Ttg-1, a gene encoding a potential zinc finger protein. Mol. Cell. Biol. 9:2124-2132.
    • (1989) Mol. Cell. Biol. , vol.9 , pp. 2124-2132
    • McGuire, E.A.1    Hockett, R.D.2    Pollock, K.M.3    Bartholdi, M.F.4    O'Brien, S.J.5    Korsmeyer, S.J.6
  • 26
    • 0028244488 scopus 로고
    • Multifactorial inheritance of neural tube defects: Localization of the major gene and recognition of modifiers in ct mutant mice
    • Neumann, P. E., W. N. Frankel, V. A. Letts, J. M. Coffin, A. J. Copp, and M. Bernfield. 1994. Multifactorial inheritance of neural tube defects: localization of the major gene and recognition of modifiers in ct mutant mice. Nat. Genet. 6:357-362.
    • (1994) Nat. Genet. , vol.6 , pp. 357-362
    • Neumann, P.E.1    Frankel, W.N.2    Letts, V.A.3    Coffin, J.M.4    Copp, A.J.5    Bernfield, M.6
  • 27
    • 0028799441 scopus 로고
    • Association of erythroid transcription factors: Complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1
    • Osada, H., G. Grutz, H. Axelson, A. Forster, and T. H. Rabbitts. 1995. Association of erythroid transcription factors: complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1. Proc. Natl. Acad. Sci. USA 92:9585-9589.
    • (1995) Proc. Natl. Acad. Sci. USA , vol.92 , pp. 9585-9589
    • Osada, H.1    Grutz, G.2    Axelson, H.3    Forster, A.4    Rabbitts, T.H.5
  • 29
    • 0032168564 scopus 로고    scopus 로고
    • LMO T-cell translocation oncogenes typify genes activated by chromosomal translocations that alter transcription and developmental processes
    • Rabbitts, T. H. 1998. LMO T-cell translocation oncogenes typify genes activated by chromosomal translocations that alter transcription and developmental processes. Genes Dev. 12:2651-2657.
    • (1998) Genes Dev. , vol.12 , pp. 2651-2657
    • Rabbitts, T.H.1
  • 30
    • 0025984266 scopus 로고
    • Translocations, master genes, and differences between the origins of acute and chronic leukemias
    • Rabbitts, T. H. 1991. Translocations, master genes, and differences between the origins of acute and chronic leukemias. Cell 67:641-644.
    • (1991) Cell , vol.67 , pp. 641-644
    • Rabbitts, T.H.1
  • 33
    • 0025933456 scopus 로고
    • TTG-2, a new gene encoding a cysteine-rich protein with the LIM motif, is overexpressed in acute T-cell leukaemia with the t(11;14)(p13;q11)
    • Royer-Pokora, B., U. Loos, and W.-D. Ludwig. 1991. TTG-2, a new gene encoding a cysteine-rich protein with the LIM motif, is overexpressed in acute T-cell leukaemia with the t(11;14)(p13;q11). Oncogene 6:1887-1893.
    • (1991) Oncogene , vol.6 , pp. 1887-1893
    • Royer-Pokora, B.1    Loos, U.2    Ludwig, W.-D.3
  • 36
    • 0016700864 scopus 로고
    • Detection of specific sequences among DNA fragments separated by gel electrophoresis
    • Southern, E. M. 1975. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. Mol. Biol. 98:503-517.
    • (1975) J. Mol. Biol. , vol.98 , pp. 503-517
    • Southern, E.M.1
  • 37
    • 0032441890 scopus 로고    scopus 로고
    • Mouse deformed epidermal autoregulatory factor 1 recruits a LIM domain factor, LMO-4, and CLIM coregulators
    • Sugihara, T. M., I. Bach, C. Kioussi, M. G. Rosenfeld, and B. Andersen. 1998. Mouse deformed epidermal autoregulatory factor 1 recruits a LIM domain factor, LMO-4, and CLIM coregulators. Proc. Natl. Acad. Sci. USA 95:15418-15423.
    • (1998) Proc. Natl. Acad. Sci. USA , vol.95 , pp. 15418-15423
    • Sugihara, T.M.1    Bach, I.2    Kioussi, C.3    Rosenfeld, M.G.4    Andersen, B.5
  • 38
    • 0023646810 scopus 로고
    • Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells
    • Thomas, K. R., and M. R. Capecchi. 1987. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51:503-512.
    • (1987) Cell , vol.51 , pp. 503-512
    • Thomas, K.R.1    Capecchi, M.R.2
  • 39
    • 0019061278 scopus 로고
    • Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose
    • Thomas, P. S. 1980. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc. Natl. Acad. Sci. USA 77:5201-5205.
    • (1980) Proc. Natl. Acad. Sci. USA , vol.77 , pp. 5201-5205
    • Thomas, P.S.1
  • 42
    • 0032542215 scopus 로고    scopus 로고
    • The LMO1 and LDB1 proteins interact in human T cell acute leukaemia with the chromosomal translocation t(11;14)(p15;q11)
    • Valge-Archer, V., A. Forster, and T. H. Rabbitts. 1998. The LMO1 and LDB1 proteins interact in human T cell acute leukaemia with the chromosomal translocation t(11;14)(p15;q11). Oncogene 17:3199-3202.
    • (1998) Oncogene , vol.17 , pp. 3199-3202
    • Valge-Archer, V.1    Forster, A.2    Rabbitts, T.H.3
  • 44
    • 0031440922 scopus 로고    scopus 로고
    • The LIM-domain binding protein Ldb1 and its partner LMO2 act as negative regulators of erythroid differentiation
    • Visvader, J. E., X. Mao, Y. Fujiwara, K. Hahm, and S. H. Orkin. 1997. The LIM-domain binding protein Ldb1 and its partner LMO2 act as negative regulators of erythroid differentiation. Proc. Natl. Acad. Sci. USA 94:13707-13712.
    • (1997) Proc. Natl. Acad. Sci. USA , vol.94 , pp. 13707-13712
    • Visvader, J.E.1    Mao, X.2    Fujiwara, Y.3    Hahm, K.4    Orkin, S.H.5
  • 47
    • 0027973545 scopus 로고
    • Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukaemia
    • Wadman, I., J. Li, R. O. Bash, A. Forster, H. Osada, T. H. Rabbitts, and R. Baer. 1994. Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukaemia. EMBO J. 13:4831-4839.
    • (1994) EMBO J. , vol.13 , pp. 4831-4839
    • Wadman, I.1    Li, J.2    Bash, R.O.3    Forster, A.4    Osada, H.5    Rabbitts, T.H.6    Baer, R.7
  • 48
    • 0030999645 scopus 로고    scopus 로고
    • The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes the TAL1, E47, GATA-1 and Ldb1/NLI proteins
    • Wadman, I. A., H. Osada, G. G. Grutz, A. D. Agulnick, H. Westphal, A. Forster, and T. H. Rabbitts. 1997. The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes the TAL1, E47, GATA-1 and Ldb1/NLI proteins. EMBO J. 16:3145-3157.
    • (1997) EMBO J. , vol.16 , pp. 3145-3157
    • Wadman, I.A.1    Osada, H.2    Grutz, G.G.3    Agulnick, A.D.4    Westphal, H.5    Forster, A.6    Rabbitts, T.H.7
  • 49
    • 0028278325 scopus 로고
    • The oncogenic cysteine-rich LIM domain protein rbm2 is essential for erythroid development
    • Warren, A. J., W. H. Colledge, M. B. L. Carlton, M. J. Evans, A. J. H. Smith, and T. H. Rabbitts. 1994. The oncogenic cysteine-rich LIM domain protein rbm2 is essential for erythroid development. Cell 78:45-58.
    • (1994) Cell , vol.78 , pp. 45-58
    • Warren, A.J.1    Colledge, W.H.2    Carlton, M.B.L.3    Evans, M.J.4    Smith, A.J.H.5    Rabbitts, T.H.6
  • 50
    • 0024043341 scopus 로고
    • mec-3, a homeobox-containing gene that specifies differentiation of the touch receptor neurons in C. elegans
    • Way, J. C., and M. Chalfie. 1988. mec-3, a homeobox-containing gene that specifies differentiation of the touch receptor neurons in C. elegans. Cell 54:5-16.
    • (1988) Cell , vol.54 , pp. 5-16
    • Way, J.C.1    Chalfie, M.2
  • 51
    • 0042121407 scopus 로고    scopus 로고
    • Two promoters within the human LMO4 gene contribute to its overexpression in breast cancer cells
    • Wittlin, S., E. Y. Sum, N. K. Jonas, G. J. Lindeman, and J. E. Visvader. 2003. Two promoters within the human LMO4 gene contribute to its overexpression in breast cancer cells. Genomics 82:280-287.
    • (2003) Genomics , vol.82 , pp. 280-287
    • Wittlin, S.1    Sum, E.Y.2    Jonas, N.K.3    Lindeman, G.J.4    Visvader, J.E.5
  • 52
    • 0037148909 scopus 로고    scopus 로고
    • The LIM-domain protein Lmo2 is a key regulator of tumour anogiogenesis: A new anti-angiogenesis drug target
    • Yamada, Y., R. Pannell, A. Forster, and T. H. Rabbitts. 2002. The LIM-domain protein Lmo2 is a key regulator of tumour anogiogenesis: a new anti-angiogenesis drug target. Oncogene 21:1309-1315.
    • (2002) Oncogene , vol.21 , pp. 1309-1315
    • Yamada, Y.1    Pannell, R.2    Forster, A.3    Rabbitts, T.H.4
  • 53
    • 0034602651 scopus 로고    scopus 로고
    • The oncogenic LIM-only transcription factor Lmo2 regulates angiogenesis but not vasculogenesis
    • Yamada, Y., R. Pannell, A. Forster, and T. H. Rabbitts. 2000. The oncogenic LIM-only transcription factor Lmo2 regulates angiogenesis but not vasculogenesis. Proc. Natl. Acad. Sci. USA 97:320-324.
    • (2000) Proc. Natl. Acad. Sci. USA , vol.97 , pp. 320-324
    • Yamada, Y.1    Pannell, R.2    Forster, A.3    Rabbitts, T.H.4
  • 55
    • 0025358272 scopus 로고
    • A mutant neomycin phosphotransferase II gene reduces the resistance of transformants to antibiotic selection pressure
    • Yenofsky, R. L., M. Fine, and J. W. Pellow. 1990. A mutant neomycin phosphotransferase II gene reduces the resistance of transformants to antibiotic selection pressure. Proc. Natl. Acad. Sci. USA 87:3435-3439.
    • (1990) Proc. Natl. Acad. Sci. USA , vol.87 , pp. 3435-3439
    • Yenofsky, R.L.1    Fine, M.2    Pellow, J.W.3
  • 56
    • 0023100760 scopus 로고
    • Cell lineages in peripheral nervous system ontogeny: Medium-induced modulation of neuronal phenotypic expression in neural crest cell cultures
    • Ziller, C., M. Fauquet, C. Kalcheim, J. Smith, and N. M. Le Douarin. 1987. Cell lineages in peripheral nervous system ontogeny: medium-induced modulation of neuronal phenotypic expression in neural crest cell cultures. Dev. Biol. 120:101-111.
    • (1987) Dev. Biol. , vol.120 , pp. 101-111
    • Ziller, C.1    Fauquet, M.2    Kalcheim, C.3    Smith, J.4    Le Douarin, N.M.5


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