0 8 Abnormal abnormal JJ 9 10 T t NN 11 21 lymphocyte lymphocyte NN 22 33 development development NN 34 41 induced induce VBN 42 44 by by IN 45 53 targeted target VBN 54 68 overexpression overexpression NN 69 71 of of IN 72 79 IkappaB IkappaB NNP 80 85 alpha alpha NN 85 86 . . . 88 89 A a DT 90 94 role role NN 95 97 in in IN 98 104 thymic thymic JJ 105 115 maturation maturation NN 116 119 for for IN 120 127 factors factor NNS 128 130 of of IN 131 134 the the DT 135 144 NF-kappaB NF-kappaB NNP 145 151 family family NN 152 155 has have VBZ 156 160 long long RB 161 165 been be VBN 166 175 suspected suspect VBN 175 176 , , , 177 180 but but CC 181 184 not not RB 185 188 yet yet RB 189 195 proven prove VBN 195 196 . . . 197 207 Transgenic transgenic JJ 208 212 mice mouse NNS 213 217 with with IN 218 219 a a DT 220 239 lymphocyte-specific lymphocyte-specific JJ 240 246 defect defect NN 247 249 in in IN 250 259 NF-kappaB NF-kappaB NNP 260 270 activation activation NN 271 275 were be VBD 276 284 produced produce VBN 285 287 by by IN 288 296 targeted target VBN 297 307 expression expression NN 308 310 of of IN 311 316 human human JJ 317 324 IkappaB IkappaB NNP 325 330 alpha alpha NN 330 331 . . . 332 335 The the DT 336 342 thymic thymic JJ 343 354 cellularity cellularity NN 355 357 of of IN 358 363 these these DT 364 368 mice mouse NNS 369 372 was be VBD 373 386 significantly significantly RB 387 396 decreased decrease VBN 396 397 . . . 398 401 The the DT 402 412 proportion proportion NN 413 415 of of IN 416 422 mature mature JJ 422 423 , , , 424 431 TCRhigh tcrhigh JJ 432 442 thymocytes thymocyte NNS 443 445 of of IN 446 449 the the DT 450 459 alphabeta alphabeta NN 460 467 lineage lineage NN 468 471 was be VBD 472 479 reduced reduce VBN 479 480 , , , 481 484 and and CC 485 488 the the DT 489 498 remaining remain VBG 499 506 TCRhigh tcrhigh JJ 507 517 population population NN 518 527 contained contain VBD 528 530 an an DT 531 540 unusually unusually RB 541 545 high high JJ 546 556 proportion proportion NN 557 559 of of IN 560 575 double-positive double-positive JJ 576 581 cells cell NNS 581 582 . . . 583 587 This this DT 588 594 defect defect NN 595 597 in in IN 598 608 maturation maturation NN 609 617 resulted result VBD 618 620 in in IN 621 622 a a DT 623 632 transgene transgene NN 633 647 dose-dependent dose-dependent JJ 648 657 reduction reduction NN 658 660 in in IN 661 671 peripheral peripheral JJ 672 673 T t NN 674 685 lymphocytes lymphocyte NNS 685 686 , , , 687 691 with with IN 692 695 the the DT 696 699 CD8 cd8 NN 700 707 lineage lineage NN 708 713 being be VBG 714 718 more more RBR 719 727 severely severely RB 728 736 affected affect VBN 736 737 . . . 738 743 These these DT 744 748 data datum NNS 749 756 provide provide VBP 757 763 direct direct JJ 764 772 evidence evidence NN 773 776 for for IN 777 780 the the DT 781 792 involvement involvement NN 793 795 of of IN 796 809 NF-kappaB/Rel NF-kappaB/Rel NNP 810 816 family family NN 817 825 proteins protein NNS 826 828 in in IN 829 833 late late JJ 834 840 stages stage NNS 841 843 of of IN 844 845 T t NN 846 856 lymphocyte lymphocyte NN 857 868 development development NN 868 869 , , , 870 880 coincident coincident JJ 881 885 with with IN 886 894 positive positive JJ 895 898 and and CC 899 907 negative negative JJ 908 917 selection selection NN 917 918 . . .