0 8 Impaired impaired JJ 9 14 fetal fetal JJ 15 24 thymocyte thymocyte NN 25 36 development development NN 37 42 after after IN 43 52 efficient efficient JJ 53 72 adenovirus-mediated adenovirus-mediated JJ 73 83 inhibition inhibition NN 84 86 of of IN 87 95 NF-kappa NF-kappa NNP 96 97 B B NNP 98 108 activation activation NN 108 109 . . . 111 113 We we PRP 114 123 introduce introduce VBP 124 125 a a DT 126 129 new new JJ 130 142 experimental experimental JJ 143 149 system system NN 150 159 combining combine VBG 160 179 adenovirus-mediated adenovirus-mediated JJ 180 184 gene gene NN 185 193 transfer transfer NN 194 197 and and CC 198 203 fetal fetal JJ 204 210 thymic thymic JJ 211 216 organ organ NN 217 224 culture culture NN 225 226 ( ( ( 226 230 FTOC FTOC NNP 230 231 ) ) ) 231 232 . . . 233 237 This this DT 238 244 system system NN 245 252 allowed allow VBD 253 255 us us PRP 256 258 to to TO 259 270 efficiently efficiently RB 271 278 express express VB 279 281 in in IN 282 292 developing develop VBG 293 303 thymocytes thymocyte NNS 304 305 a a DT 306 312 mutant mutant JJ 313 317 form form NN 318 320 of of IN 321 324 the the DT 325 333 NF-kappa NF-kappa NNP 334 335 B B NNP 336 345 inhibitor inhibitor NN 346 347 I i NN 348 353 kappa kappa NN 354 355 B B NNP 356 361 alpha alpha NN 362 363 ( ( ( 363 368 mut-I mut-i NN 369 374 kappa kappa NN 375 376 B B NNP 376 377 ) ) ) 378 381 and and CC 382 384 to to TO 385 390 study study VB 391 394 the the DT 395 405 maturation maturation NN 406 413 defects defect NNS 414 423 occurring occur VBG 424 428 when when WRB 429 437 NF-kappa NF-kappa NNP 438 439 B B NNP 440 450 activation activation NN 451 453 is be VBZ 454 463 inhibited inhibit VBN 464 470 during during IN 471 476 fetal fetal JJ 477 488 development development NN 488 489 . . . 490 495 Fetal fetal JJ 496 506 thymocytes thymocyte NNS 507 515 infected infect VBN 516 520 with with IN 521 531 adenovirus adenovirus NN 532 542 containing contain VBG 543 548 mut-I mut-I NNP 549 554 kappa kappa NN 555 556 B B NNP 557 561 were be VBD 562 567 found find VBN 568 570 to to TO 571 578 develop develop VB 579 587 normally normally RB 588 593 until until IN 594 597 the the DT 598 608 CD44-CD25+ cd44-cd25+ JJ 608 609 , , , 610 618 CD4-CD8- cd4-cd8- JJ 619 634 double-negative double-negative JJ 635 640 stage stage NN 640 641 , , , 642 647 while while IN 648 658 production production NN 659 661 of of IN 662 666 more more RBR 667 673 mature mature JJ 674 689 double-positive double-positive JJ 690 693 and and CC 694 709 single-positive single-positive JJ 710 721 populations population NNS 722 725 was be VBD 726 734 strongly strongly RB 735 744 decreased decrease VBN 744 745 . . . 746 759 Proliferation proliferation NN 759 760 , , , 761 763 as as IN 764 772 measured measure VBN 773 775 by by IN 776 779 the the DT 780 790 percentage percentage NN 791 793 of of IN 794 799 cells cell NNS 800 802 in in IN 803 808 cycle cycle NN 809 817 appeared appear VBD 818 824 normal normal JJ 824 825 , , , 826 828 as as IN 829 832 did do VBD 833 846 rearrangement rearrangement NN 847 850 and and CC 851 861 expression expression NN 862 864 of of IN 865 868 the the DT 869 872 TCR TCR NNP 873 883 beta-chain beta-chain NN 883 884 . . . 885 892 However however RB 892 893 , , , 894 903 apoptosis apoptosis NN 904 907 was be VBD 908 912 much much RB 913 919 higher high JJR 920 922 in in IN 923 927 FTOC FTOC NNP 928 936 infected infect VBN 937 941 with with IN 942 952 adenovirus adenovirus NN 953 963 containing contain VBG 964 969 mut-I mut-i NN 970 975 kappa kappa NN 976 977 B B NNP 978 982 than than IN 983 985 in in IN 986 990 FTOC FTOC NNP 991 999 infected infect VBN 1000 1004 with with IN 1005 1006 a a DT 1007 1014 control control NN 1015 1020 virus virus NN 1020 1021 . . . 1022 1027 Taken take VBN 1028 1036 together together RB 1036 1037 , , , 1038 1043 these these DT 1044 1051 results result NNS 1052 1059 suggest suggest VBP 1060 1064 that that IN 1065 1073 NF-kappa NF-kappa NNP 1074 1075 B B NNP 1076 1081 plays play VBZ 1082 1083 a a DT 1084 1091 crucial crucial JJ 1092 1096 role role NN 1097 1099 in in IN 1100 1108 ensuring ensure VBG 1109 1112 the the DT 1113 1128 differentiation differentiation NN 1129 1132 and and CC 1133 1141 survival survival NN 1142 1144 of of IN 1145 1155 thymocytes thymocyte NNS 1156 1158 in in IN 1159 1162 the the DT 1163 1168 early early JJ 1169 1175 stages stage NNS 1176 1178 of of IN 1179 1184 their their PRP$ 1185 1196 development development NN 1196 1197 . . .