0 6 Tissue tissue NN 7 10 and and CC 11 20 cell-type cell-type JJ 21 29 specific specific JJ 30 40 expression expression NN 41 43 of of IN 44 47 the the DT 48 56 tuberous tuberous JJ 57 66 sclerosis sclerosis NN 67 71 gene gene NN 71 72 , , , 73 77 TSC2 TSC2 NNP 77 78 , , , 79 81 in in IN 82 87 human human JJ 88 95 tissues tissue NNS 95 96 . . . 98 102 TSC2 TSC2 NNP 103 105 is be VBZ 106 107 a a DT 108 112 gene gene NN 113 115 on on IN 116 126 chromosome chromosome NN 127 134 16p13.3 16p13.3 NN 135 145 associated associate VBN 146 150 with with IN 151 154 the the DT 155 164 autosomal autosomal JJ 165 173 dominant dominant JJ 174 188 neurocutaneous neurocutaneous JJ 189 197 disorder disorder NN 197 198 , , , 199 207 tuberous tuberous JJ 208 217 sclerosis sclerosis NN 218 225 complex complex NN 226 227 ( ( ( 227 230 TSC TSC NNP 230 231 ) ) ) 231 232 . . . 233 235 By by IN 236 241 using use VBG 242 243 a a DT 244 251 partial partial JJ 252 262 nucleotide nucleotide NN 263 271 sequence sequence NN 272 276 from from IN 277 280 the the DT 281 287 cloned clone VBN 288 292 TSC2 tsc2 NN 293 296 and and CC 297 307 polymerase polymerase NN 308 313 chain chain NN 314 322 reaction reaction NN 323 334 methodology methodology NN 334 335 , , , 336 338 we we PRP 339 350 constructed construct VBD 351 352 a a DT 353 372 digoxigenin-labeled digoxigenin-labeled JJ 373 386 complementary complementary JJ 387 390 DNA dna NN 391 396 probe probe NN 397 399 to to TO 400 407 examine examine VB 408 412 TSC2 tsc2 NN 413 417 gene gene NN 418 428 expression expression NN 429 431 in in IN 432 440 autopsy- autopsy- NN 441 443 or or CC 444 458 biopsy-derived biopsy-derived JJ 459 464 human human JJ 465 472 tissues tissue NNS 473 475 by by IN 476 478 in in FW 479 483 situ situ FW 484 497 hybridization hybridization NN 497 498 . . . 499 503 TSC2 tsc2 NN 504 513 messenger messenger NN 514 517 RNA RNA NNP 518 521 was be VBD 522 528 widely widely RB 529 538 expressed express VBN 539 541 in in IN 542 549 various various JJ 550 554 cell cell NN 555 560 types type NNS 561 571 throughout throughout IN 572 575 the the DT 576 580 body body NN 580 581 , , , 582 591 including include VBG 592 601 epithelia epithelia NN 601 602 , , , 603 614 lymphocytes lymphocyte NNS 614 615 , , , 616 619 and and CC 620 625 cells cell NNS 626 630 with with IN 631 640 endocrine endocrine JJ 641 650 functions function NNS 650 651 , , , 652 656 e.g. e.g. FW 656 657 , , , 658 665 adrenal adrenal JJ 666 672 cortex cortex NN 673 676 and and CC 677 685 anterior anterior JJ 686 695 pituitary pituitary NN 695 696 . . . 697 699 It it PRP 700 703 was be VBD 704 715 prominently prominently RB 716 719 and and CC 720 731 selectively selectively RB 732 733 ( ( ( 733 739 within within IN 740 743 the the DT 744 751 central central JJ 752 759 nervous nervous JJ 760 766 system system NN 766 767 ) ) ) 768 777 expressed express VBN 778 780 in in IN 781 790 pyramidal pyramidal JJ 791 796 cells cell NNS 797 799 of of IN 800 803 the the DT 804 812 cerebral cerebral JJ 813 819 cortex cortex NN 820 823 and and CC 824 829 other other JJ 830 835 motor motor NN 836 843 neurons neuron NNS 843 844 , , , 845 849 e.g. e.g. FW 849 850 , , , 851 853 in in IN 854 860 spinal spinal JJ 861 865 cord cord NN 866 869 and and CC 870 879 brainstem brainstem NN 880 886 nuclei nucleus NNS 886 887 . . . 888 896 Visceral visceral JJ 897 901 TSC2 TSC2 NNP 902 912 expression expression NN 913 916 was be VBD 917 927 comparable comparable JJ 928 930 in in IN 931 938 autopsy autopsy NN 939 946 tissues tissue NNS 947 951 from from IN 952 960 patients patient NNS 961 965 with with IN 966 969 and and CC 970 977 without without IN 978 981 TSC TSC NNP 981 982 ; ; : 983 987 TSC2 tsc2 NN 988 997 messenger messenger NN 998 1001 RNA RNA NNP 1002 1012 expression expression NN 1013 1016 was be VBD 1017 1021 most most RBS 1022 1031 prominent prominent JJ 1032 1034 in in IN 1035 1040 cells cell NNS 1041 1045 with with IN 1046 1047 a a DT 1048 1053 rapid rapid JJ 1054 1061 mitotic mitotic JJ 1062 1066 rate rate NN 1067 1070 and and CC 1071 1079 turnover turnover NN 1079 1080 , , , 1081 1085 e.g. e.g. FW 1085 1086 , , , 1087 1096 epithelia epithelia NN 1097 1100 and and CC 1101 1112 lymphocytes lymphocyte NNS 1112 1113 , , , 1114 1118 with with IN 1119 1126 central central JJ 1127 1134 nervous nervous JJ 1135 1141 system system NN 1142 1151 pyramidal pyramidal JJ 1152 1157 cells cell NNS 1158 1161 and and CC 1162 1167 other other JJ 1168 1175 neurons neuron NNS 1176 1181 being be VBG 1182 1184 an an DT 1185 1192 obvious obvious JJ 1193 1202 exception exception NN 1202 1203 , , , 1204 1210 and/or and/or CC 1211 1213 in in IN 1214 1219 cells cell NNS 1220 1224 with with IN 1225 1234 important important JJ 1235 1254 secretory/transport secretory/transport NN 1255 1264 functions function NNS 1264 1265 . . . 1266 1270 This this DT 1271 1281 widespread widespread JJ 1282 1292 expression expression NN 1293 1295 of of IN 1296 1299 the the DT 1300 1304 TSC2 tsc2 NN 1305 1309 gene gene NN 1310 1318 supports support VBZ 1319 1322 the the DT 1323 1327 view view NN 1328 1332 that that IN 1333 1335 it it PRP 1336 1343 encodes encode VBZ 1344 1345 a a DT 1346 1353 protein protein NN 1354 1359 vital vital JJ 1360 1362 to to TO 1363 1367 cell cell NN 1368 1374 growth growth NN 1375 1378 and and CC 1379 1389 metabolism metabolism NN 1390 1392 or or CC 1393 1396 one one CD 1397 1401 that that WDT 1402 1411 functions function VBZ 1412 1414 as as IN 1415 1416 a a DT 1417 1429 tumor/growth tumor/growth NN 1430 1440 suppressor suppressor NN 1440 1441 . . .