PMC:1084331 / 7752-9744 JSONTXT

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1 Replacement of Er81 by EWS-Pea3\n(A) Generation of Er81EWS-Pea3 mutant mice. Above is the organization of the Er81 genomic locus in the region targeted by homologous recombination in analogy to [14]. Exons 1–4 are shown as light blue boxes, and the Er81 start codon in exon 2 is indicated as ATG. The probe used to detect homologous recombination is shown as a grey box. Below is replacement of Er81 by EWS-Pea3 through the integration of EWS-Pea3 in frame with the endogenous start codon of the Er81 locus in exon 2 (in analogy to [14]).\n(B) PCR and Southern blot analysis of Er81EWS-Pea3 wild-type (+/+), heterozygous (+/−), and homozygous (−/−) genomic DNA to detect the mutant allele. PCR primer pairs (EWS-Pea3ki) were used to detect specifically the recombined allele, and a primer pair in exon2 was used to detect the presence of the wild-type allele [14].\n(C–E) Analysis of Er81 expression in lumbar DRG neurons of E16.5 wild-type (C), Er81−/− (D), and Er81EWS-Pea3/− (E) embryos. Inset in lower right corner of each panel shows Isl1 expression in the respective DRG.\n(F–H) PV expression in lumbar DRG of E16.5 wild-type (F), Er81−/− (G), and Er81EWS-Pea3/− (H) embryos. Confocal scans were performed with equal gain intensity.\n(J) Transcriptional transactivation of luciferase expression from a minimal reporter construct containing five consensus ETS DNA-binding sites ( GCCGGAAGC; [18,19]) and a minimal TK promoter upon transient transfection of Er81 (n ≥ 7; 3.03 ± 0.66) or EWS-Pea3 (n ≥ 7; 20.3 ± 2.7). Relative luciferase activity normalized to control (Con).\nScale bar: 80 μm. Expression of Er81 in DRG neurons of embryos containing integration of EWS-Pea3 in the Er81 locus (Er81EWS-Pea3/−) was abolished (Figure 1E), and the expression level of the calcium-binding protein Parvalbumin (PV) in proprioceptive afferents, which is decreased approximately 5- to 10-fold in Er81 mutants [14], was comparable to wild-type levels in Er81EWS-Pea3/− embryos (Figure 1F–1H)."}

{"project":"craft-ca-core-ex-dev","denotations":[{"id":"T3450","span":{"begin":1603,"end":1613},"obj":"GO:0010467"},{"id":"T3451","span":{"begin":1617,"end":1621},"obj":"PR_EXT:000007223"},{"id":"T3452","span":{"begin":1625,"end":1628},"obj":"UBERON:0000044"},{"id":"T3453","span":{"begin":1629,"end":1636},"obj":"CL:0000540"},{"id":"T3454","span":{"begin":1640,"end":1647},"obj":"UBERON:0000922"},{"id":"T3455","span":{"begin":1674,"end":1677},"obj":"PR_EXT:000007243"},{"id":"T3456","span":{"begin":1678,"end":1682},"obj":"PR_EXT:000007227"},{"id":"T3457","span":{"begin":1690,"end":1694},"obj":"PR_EXT:000007223"},{"id":"T3458","span":{"begin":1702,"end":1706},"obj":"PR_EXT:000007223"},{"id":"T3459","span":{"begin":1706,"end":1709},"obj":"PR_EXT:000007243"},{"id":"T3460","span":{"begin":1710,"end":1714},"obj":"PR_EXT:000007227"},{"id":"T3461","span":{"begin":1715,"end":1716},"obj":"SO_EXT:sequence_nullness_or_absence"},{"id":"T3462","span":{"begin":1753,"end":1763},"obj":"GO:0010467"},{"id":"T3463","span":{"begin":1777,"end":1784},"obj":"CHEBI_EXT:calcium"},{"id":"T3464","span":{"begin":1785,"end":1792},"obj":"CHEMINF_GO_EXT:chemical_binding_or_bond_formation"},{"id":"T3465","span":{"begin":1793,"end":1800},"obj":"CHEBI_PR_EXT:protein"},{"id":"T3466","span":{"begin":1801,"end":1812},"obj":"PR_EXT:000013502"},{"id":"T3467","span":{"begin":1814,"end":1816},"obj":"PR_EXT:000013502"},{"id":"T3468","span":{"begin":1821,"end":1835},"obj":"GO:0019230"},{"id":"T3469","span":{"begin":1897,"end":1901},"obj":"PR_EXT:000007223"},{"id":"T3470","span":{"begin":1902,"end":1909},"obj":"SO_EXT:sequence_altered_entity"},{"id":"T3471","span":{"begin":1934,"end":1943},"obj":"SO_EXT:wild_type_entity_or_quality"},{"id":"T3472","span":{"begin":1954,"end":1958},"obj":"PR_EXT:000007223"},{"id":"T3473","span":{"begin":1958,"end":1961},"obj":"PR_EXT:000007243"},{"id":"T3474","span":{"begin":1962,"end":1966},"obj":"PR_EXT:000007227"},{"id":"T3475","span":{"begin":1967,"end":1968},"obj":"SO_EXT:sequence_nullness_or_absence"},{"id":"T3476","span":{"begin":1969,"end":1976},"obj":"UBERON:0000922"}],"text":"\nFigure 1 Replacement of Er81 by EWS-Pea3\n(A) Generation of Er81EWS-Pea3 mutant mice. Above is the organization of the Er81 genomic locus in the region targeted by homologous recombination in analogy to [14]. Exons 1–4 are shown as light blue boxes, and the Er81 start codon in exon 2 is indicated as ATG. The probe used to detect homologous recombination is shown as a grey box. Below is replacement of Er81 by EWS-Pea3 through the integration of EWS-Pea3 in frame with the endogenous start codon of the Er81 locus in exon 2 (in analogy to [14]).\n(B) PCR and Southern blot analysis of Er81EWS-Pea3 wild-type (+/+), heterozygous (+/−), and homozygous (−/−) genomic DNA to detect the mutant allele. PCR primer pairs (EWS-Pea3ki) were used to detect specifically the recombined allele, and a primer pair in exon2 was used to detect the presence of the wild-type allele [14].\n(C–E) Analysis of Er81 expression in lumbar DRG neurons of E16.5 wild-type (C), Er81−/− (D), and Er81EWS-Pea3/− (E) embryos. Inset in lower right corner of each panel shows Isl1 expression in the respective DRG.\n(F–H) PV expression in lumbar DRG of E16.5 wild-type (F), Er81−/− (G), and Er81EWS-Pea3/− (H) embryos. Confocal scans were performed with equal gain intensity.\n(J) Transcriptional transactivation of luciferase expression from a minimal reporter construct containing five consensus ETS DNA-binding sites ( GCCGGAAGC; [18,19]) and a minimal TK promoter upon transient transfection of Er81 (n ≥ 7; 3.03 ± 0.66) or EWS-Pea3 (n ≥ 7; 20.3 ± 2.7). Relative luciferase activity normalized to control (Con).\nScale bar: 80 μm. Expression of Er81 in DRG neurons of embryos containing integration of EWS-Pea3 in the Er81 locus (Er81EWS-Pea3/−) was abolished (Figure 1E), and the expression level of the calcium-binding protein Parvalbumin (PV) in proprioceptive afferents, which is decreased approximately 5- to 10-fold in Er81 mutants [14], was comparable to wild-type levels in Er81EWS-Pea3/− embryos (Figure 1F–1H)."}

{"project":"2_test","denotations":[{"id":"15836427-10850491-84719628","span":{"begin":205,"end":207},"obj":"10850491"},{"id":"15836427-10850491-84719629","span":{"begin":543,"end":545},"obj":"10850491"},{"id":"15836427-10850491-84719630","span":{"begin":869,"end":871},"obj":"10850491"},{"id":"15836427-9734357-84719631","span":{"begin":1403,"end":1405},"obj":"9734357"},{"id":"15836427-11096072-84719632","span":{"begin":1406,"end":1408},"obj":"11096072"},{"id":"15836427-10850491-84719633","span":{"begin":1911,"end":1913},"obj":"10850491"},{"id":"T40480","span":{"begin":205,"end":207},"obj":"10850491"},{"id":"T21606","span":{"begin":543,"end":545},"obj":"10850491"},{"id":"T94600","span":{"begin":869,"end":871},"obj":"10850491"},{"id":"T96846","span":{"begin":1403,"end":1405},"obj":"9734357"},{"id":"T64151","span":{"begin":1406,"end":1408},"obj":"11096072"},{"id":"T5880","span":{"begin":1911,"end":1913},"obj":"10850491"}],"text":"\nFigure 1 Replacement of Er81 by EWS-Pea3\n(A) Generation of Er81EWS-Pea3 mutant mice. Above is the organization of the Er81 genomic locus in the region targeted by homologous recombination in analogy to [14]. Exons 1–4 are shown as light blue boxes, and the Er81 start codon in exon 2 is indicated as ATG. The probe used to detect homologous recombination is shown as a grey box. Below is replacement of Er81 by EWS-Pea3 through the integration of EWS-Pea3 in frame with the endogenous start codon of the Er81 locus in exon 2 (in analogy to [14]).\n(B) PCR and Southern blot analysis of Er81EWS-Pea3 wild-type (+/+), heterozygous (+/−), and homozygous (−/−) genomic DNA to detect the mutant allele. PCR primer pairs (EWS-Pea3ki) were used to detect specifically the recombined allele, and a primer pair in exon2 was used to detect the presence of the wild-type allele [14].\n(C–E) Analysis of Er81 expression in lumbar DRG neurons of E16.5 wild-type (C), Er81−/− (D), and Er81EWS-Pea3/− (E) embryos. Inset in lower right corner of each panel shows Isl1 expression in the respective DRG.\n(F–H) PV expression in lumbar DRG of E16.5 wild-type (F), Er81−/− (G), and Er81EWS-Pea3/− (H) embryos. Confocal scans were performed with equal gain intensity.\n(J) Transcriptional transactivation of luciferase expression from a minimal reporter construct containing five consensus ETS DNA-binding sites ( GCCGGAAGC; [18,19]) and a minimal TK promoter upon transient transfection of Er81 (n ≥ 7; 3.03 ± 0.66) or EWS-Pea3 (n ≥ 7; 20.3 ± 2.7). Relative luciferase activity normalized to control (Con).\nScale bar: 80 μm. Expression of Er81 in DRG neurons of embryos containing integration of EWS-Pea3 in the Er81 locus (Er81EWS-Pea3/−) was abolished (Figure 1E), and the expression level of the calcium-binding protein Parvalbumin (PV) in proprioceptive afferents, which is decreased approximately 5- to 10-fold in Er81 mutants [14], was comparable to wild-type levels in Er81EWS-Pea3/− embryos (Figure 1F–1H)."}

{"project":"biosemtest","denotations":[{"id":"T2737","span":{"begin":1885,"end":1887},"obj":"UMLS/C0319022"},{"id":"T2738","span":{"begin":1933,"end":1935},"obj":"UMLS/C0319022"},{"id":"T2747","span":{"begin":1625,"end":1628},"obj":"UMLS/C1537672"},{"id":"T2757","span":{"begin":1803,"end":1814},"obj":"UMLS/C0030616"},{"id":"T2760","span":{"begin":1936,"end":1945},"obj":"UMLS/C1883559"},{"id":"T2772","span":{"begin":1603,"end":1613},"obj":"UMLS/C0017262"},{"id":"T2773","span":{"begin":1755,"end":1765},"obj":"UMLS/C0017262"},{"id":"T2805","span":{"begin":1779,"end":1802},"obj":"UP/P06495"},{"id":"T2810","span":{"begin":1904,"end":1911},"obj":"UMLS/C0596988"},{"id":"T2825","span":{"begin":1603,"end":1613},"obj":"UMLS/C0185117"},{"id":"T2826","span":{"begin":1755,"end":1765},"obj":"UMLS/C0185117"},{"id":"T2835","span":{"begin":1766,"end":1771},"obj":"UMLS/C0441889"},{"id":"T2836","span":{"begin":1946,"end":1952},"obj":"UMLS/C0441889"},{"id":"T2843","span":{"begin":1803,"end":1814},"obj":"UP/P35491"},{"id":"T2845","span":{"begin":1766,"end":1771},"obj":"UMLS/C0456079"},{"id":"T2846","span":{"begin":1946,"end":1952},"obj":"UMLS/C0456079"},{"id":"T2858","span":{"begin":1858,"end":1867},"obj":"UMLS/C0442797"},{"id":"T2892","span":{"begin":1779,"end":1802},"obj":"UMLS/C0006732"},{"id":"T2914","span":{"begin":1640,"end":1647},"obj":"UMLS/C0013935"},{"id":"T2915","span":{"begin":1973,"end":1980},"obj":"UMLS/C0013935"},{"id":"T2918","span":{"begin":1858,"end":1867},"obj":"UMLS/C0205216"},{"id":"T2931","span":{"begin":1648,"end":1658},"obj":"UMLS/C1549781"},{"id":"T2938","span":{"begin":1648,"end":1658},"obj":"UMLS/C2700400"},{"id":"T2956","span":{"begin":1648,"end":1658},"obj":"UMLS/C0332256"},{"id":"T2957","span":{"begin":1803,"end":1814},"obj":"UMLS/C1419140"},{"id":"T2963","span":{"begin":1779,"end":1802},"obj":"UP/P13566"},{"id":"T2965","span":{"begin":1625,"end":1628},"obj":"UMLS/C0011928"},{"id":"T2973","span":{"begin":1868,"end":1881},"obj":"UMLS/C0332232"},{"id":"T2978","span":{"begin":1838,"end":1847},"obj":"UMLS/C0205115"},{"id":"T3015","span":{"begin":1858,"end":1867},"obj":"UMLS/C0392756"},{"id":"T3037","span":{"begin":1779,"end":1802},"obj":"UP/P38505"},{"id":"T3053","span":{"begin":1695,"end":1700},"obj":"UMLS/C1708726"},{"id":"T3067","span":{"begin":1858,"end":1867},"obj":"UMLS/C0547047"},{"id":"T3092","span":{"begin":1640,"end":1647},"obj":"UMLS/C1305370"},{"id":"T3093","span":{"begin":1973,"end":1980},"obj":"UMLS/C1305370"},{"id":"T3115","span":{"begin":1629,"end":1636},"obj":"UMLS/C0027882"},{"id":"T3142","span":{"begin":1625,"end":1628},"obj":"UMLS/C1414151"},{"id":"T3151","span":{"begin":1659,"end":1670},"obj":"UMLS/C1158478"},{"id":"T3196","span":{"begin":1659,"end":1670},"obj":"UMLS/C1705422"},{"id":"T3221","span":{"begin":1779,"end":1802},"obj":"UMLS/C1822659"},{"id":"T3222","span":{"begin":1779,"end":1802},"obj":"UP/O42720"}],"text":"\nFigure 1 Replacement of Er81 by EWS-Pea3\n(A) Generation of Er81EWS-Pea3 mutant mice. Above is the organization of the Er81 genomic locus in the region targeted by homologous recombination in analogy to [14]. Exons 1–4 are shown as light blue boxes, and the Er81 start codon in exon 2 is indicated as ATG. The probe used to detect homologous recombination is shown as a grey box. Below is replacement of Er81 by EWS-Pea3 through the integration of EWS-Pea3 in frame with the endogenous start codon of the Er81 locus in exon 2 (in analogy to [14]).\n(B) PCR and Southern blot analysis of Er81EWS-Pea3 wild-type (+/+), heterozygous (+/−), and homozygous (−/−) genomic DNA to detect the mutant allele. PCR primer pairs (EWS-Pea3ki) were used to detect specifically the recombined allele, and a primer pair in exon2 was used to detect the presence of the wild-type allele [14].\n(C–E) Analysis of Er81 expression in lumbar DRG neurons of E16.5 wild-type (C), Er81−/− (D), and Er81EWS-Pea3/− (E) embryos. Inset in lower right corner of each panel shows Isl1 expression in the respective DRG.\n(F–H) PV expression in lumbar DRG of E16.5 wild-type (F), Er81−/− (G), and Er81EWS-Pea3/− (H) embryos. Confocal scans were performed with equal gain intensity.\n(J) Transcriptional transactivation of luciferase expression from a minimal reporter construct containing five consensus ETS DNA-binding sites ( GCCGGAAGC; [18,19]) and a minimal TK promoter upon transient transfection of Er81 (n ≥ 7; 3.03 ± 0.66) or EWS-Pea3 (n ≥ 7; 20.3 ± 2.7). Relative luciferase activity normalized to control (Con).\nScale bar: 80 μm. Expression of Er81 in DRG neurons of embryos containing integration of EWS-Pea3 in the Er81 locus (Er81EWS-Pea3/−) was abolished (Figure 1E), and the expression level of the calcium-binding protein Parvalbumin (PV) in proprioceptive afferents, which is decreased approximately 5- to 10-fold in Er81 mutants [14], was comparable to wild-type levels in Er81EWS-Pea3/− embryos (Figure 1F–1H)."}

{"project":"craft-ca-core-dev","denotations":[{"id":"T3267","span":{"begin":1603,"end":1613},"obj":"GO:0010467"},{"id":"T3268","span":{"begin":1617,"end":1621},"obj":"PR:000007223"},{"id":"T3269","span":{"begin":1625,"end":1628},"obj":"UBERON:0000044"},{"id":"T3270","span":{"begin":1629,"end":1636},"obj":"CL:0000540"},{"id":"T3271","span":{"begin":1640,"end":1647},"obj":"UBERON:0000922"},{"id":"T3272","span":{"begin":1674,"end":1677},"obj":"PR:000007243"},{"id":"T3273","span":{"begin":1678,"end":1682},"obj":"PR:000007227"},{"id":"T3274","span":{"begin":1690,"end":1694},"obj":"PR:000007223"},{"id":"T3275","span":{"begin":1702,"end":1706},"obj":"PR:000007223"},{"id":"T3276","span":{"begin":1706,"end":1709},"obj":"PR:000007243"},{"id":"T3277","span":{"begin":1710,"end":1714},"obj":"PR:000007227"},{"id":"T3278","span":{"begin":1753,"end":1763},"obj":"GO:0010467"},{"id":"T3279","span":{"begin":1801,"end":1812},"obj":"PR:000013502"},{"id":"T3280","span":{"begin":1814,"end":1816},"obj":"PR:000013502"},{"id":"T3281","span":{"begin":1821,"end":1835},"obj":"GO:0019230"},{"id":"T3282","span":{"begin":1897,"end":1901},"obj":"PR:000007223"},{"id":"T3283","span":{"begin":1954,"end":1958},"obj":"PR:000007223"},{"id":"T3284","span":{"begin":1958,"end":1961},"obj":"PR:000007243"},{"id":"T3285","span":{"begin":1962,"end":1966},"obj":"PR:000007227"},{"id":"T3286","span":{"begin":1969,"end":1976},"obj":"UBERON:0000922"}],"text":"\nFigure 1 Replacement of Er81 by EWS-Pea3\n(A) Generation of Er81EWS-Pea3 mutant mice. Above is the organization of the Er81 genomic locus in the region targeted by homologous recombination in analogy to [14]. Exons 1–4 are shown as light blue boxes, and the Er81 start codon in exon 2 is indicated as ATG. The probe used to detect homologous recombination is shown as a grey box. Below is replacement of Er81 by EWS-Pea3 through the integration of EWS-Pea3 in frame with the endogenous start codon of the Er81 locus in exon 2 (in analogy to [14]).\n(B) PCR and Southern blot analysis of Er81EWS-Pea3 wild-type (+/+), heterozygous (+/−), and homozygous (−/−) genomic DNA to detect the mutant allele. PCR primer pairs (EWS-Pea3ki) were used to detect specifically the recombined allele, and a primer pair in exon2 was used to detect the presence of the wild-type allele [14].\n(C–E) Analysis of Er81 expression in lumbar DRG neurons of E16.5 wild-type (C), Er81−/− (D), and Er81EWS-Pea3/− (E) embryos. Inset in lower right corner of each panel shows Isl1 expression in the respective DRG.\n(F–H) PV expression in lumbar DRG of E16.5 wild-type (F), Er81−/− (G), and Er81EWS-Pea3/− (H) embryos. Confocal scans were performed with equal gain intensity.\n(J) Transcriptional transactivation of luciferase expression from a minimal reporter construct containing five consensus ETS DNA-binding sites ( GCCGGAAGC; [18,19]) and a minimal TK promoter upon transient transfection of Er81 (n ≥ 7; 3.03 ± 0.66) or EWS-Pea3 (n ≥ 7; 20.3 ± 2.7). Relative luciferase activity normalized to control (Con).\nScale bar: 80 μm. Expression of Er81 in DRG neurons of embryos containing integration of EWS-Pea3 in the Er81 locus (Er81EWS-Pea3/−) was abolished (Figure 1E), and the expression level of the calcium-binding protein Parvalbumin (PV) in proprioceptive afferents, which is decreased approximately 5- to 10-fold in Er81 mutants [14], was comparable to wild-type levels in Er81EWS-Pea3/− embryos (Figure 1F–1H)."}