A mouse model of tuberous sclerosis: Neuronal loss of Tsc1 causes dysplastic and ectopic neurons, reduced myelination, seizure activity, and limited survival

Journal of Neuroscience

Volumn 27, Issue 21, 2007, Pages 5546-5558

  Meikle, Lynsey ^a   Talos, Delia M ^b   Onda, Hiroaki ^a,d   Pollizzi, Kristen ^a   Rotenberg, Alexander ^b   Sahin, Mustafa ^b   Jensen, Frances E ^b,c   Kwiatkowski, David J ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c BOSTON CHILDREN S HOSPITAL   (United States)

^d JACKSON LABORATORY   (United States)

Author keywords

Dysplastic neuron; Ectopic neurons; mTOR; Seizures; TSC1; Tuberous sclerosis

Indexed keywords

ANIMAL CELL; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DISEASE FREE SURVIVAL; EMBRYO DEVELOPMENT; FEMALE; GENE; GENE DELETION; GENE EXPRESSION; GENETIC ENGINEERING; GENETIC RECOMBINATION; MALE; MOUSE; MYELINATION; NERVE CELL; NONHUMAN; PERINATAL PERIOD; PRIORITY JOURNAL; SEIZURE; TSC1 GENE; TUBEROUS SCLEROSIS; ANIMAL; C57BL MOUSE; CBA MOUSE; COMPARATIVE STUDY; DEMYELINATING DISEASE; DISEASE MODEL; GENETICS; METABOLISM; MORTALITY; PATHOLOGY; PHYSIOLOGY; SURVIVAL RATE; TRANSGENIC MOUSE;

TUBEROUS SCLEROSIS COMPLEX 1 PROTEIN; TUMOR SUPPRESSOR PROTEIN; UNCLASSIFIED DRUG;

ANIMALS; DEMYELINATING DISEASES; DISEASE MODELS, ANIMAL; FEMALE; MALE; MICE; MICE, INBRED C57BL; MICE, INBRED CBA; MICE, TRANSGENIC; NEURONS; SEIZURES; SURVIVAL RATE; TUBEROUS SCLEROSIS; TUMOR SUPPRESSOR PROTEINS;

EID: 34250626014     PISSN: 02706474     EISSN: 02706474     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.5540-06.2007     Document Type: Article

References (63)

1. Arseni C, Alexianu M, Horvat L, Alexianu D, Petrovici A (1972) Fine structure of atypical cells in tuberous sclerosis. Acta Neuropathol (Berl) 21:185-193.
2. Astrinidis A, Henske EP (2005) Tuberous sclerosis complex: linking growth energy signaling pathways with human disease. Oncogene 24:7475-7481.
3. Astrinidis A, Cash TP, Hunter DS, Walker CL, Chernoff J, Henske EP (2002) Tuberin, the tuberous sclerosis complex 2 tumor suppressor gene product, regulates Rho activation, cell adhesion and migration. Oncogene 21:8470-8476.
4. Barres BA, Raff MC (1999) Axonal control of oligodendrocyte development. J Cell Biol 147:1123-1128.
5. Baybis M, Yu J, Lee A, Golden JA, Weiner H, McKhann G, Aronica E, Crino PB (2004) mTOR cascade activation distinguishes tubers from focal cortical dysplasia. Ann Neurol 56:478-487.
6. Benowitz LI, Routtenberg A (1997) GAP-43: an intrinsic determinant of neuronal development plasticity. Trends Neurosci 20:84-91.
7. Benvenuto G, Li S, Brown SJ, Braverman R, Vass WC, Cheadle JP, Halley DJ, Sampson JR, Wienecke R, DeClue JE (2000) The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination. Oncogene 19:6306-6316.
8. Boggs JM, Wang H, Gao W, Arvanitis DN, Gong Y, Min W (2004) A glycosynapse in myelin? Glycoconj J 21:97-110.
9. Boiko T, Winckler B (2006) Myelin under construction - teamwork required. J Cell Biol 172:799-801.
10. Chan JA, Zhang H, Roberts PS, Jozwiak S, Wieslawa G, Lewin-Kowalik J, Kotulska K, Kwiatkowski DJ (2004) Pathogenesis of tuberous sclerosis subependymal giant cell astrocytomas: biallelic inactivation of TSC1 or TSC2 leads to mTOR activation. J Neuropath Exp Neurol 63:1236-1242.
11. Cheadle JP, Reeve MP, Sampson JR, Kwiatkowski DJ (2000) Molecular genetic advances in tuberous sclerosis. Hum Genet 107:97-114.
12. Chong-Kopera H, Inoki K, Li Y, Zhu T, Garcia-Gonzalo FR, Rosa JL, Guan KL (2006) TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 the HERC1 ubiquitin ligase. J Biol Chem 281:8313-8316.
13. Cota D, Proulx K, Smith KA, Kozma SC, Thomas G, Woods SC, Seeley RJ (2006) Hypothalamic mTOR signaling regulates food intake. Science 312:927-930.
14. Crino PB (2004) Molecular pathogenesis of tuber formation in tuberous sclerosis complex. J Child Neurol 19:716-725.
15. Curatolo P (2003) Tuberous sclerosis complex: from basic science to clinical phenotypes. Cambridge, UK: Mac Keith.
16. da Silva AV, Regondi MC, Cavalheiro EA, Spreafico R (2005) Disruption of cortical development as a consequence of repetitive pilocarpine-induced status epilepticus in rats. Epilepsia 46 [Suppl 5]:22-30.
17. de Vries P, Humphrey A, McCartney D, Prather P, Bolton P, Hunt A (2005) Consensus clinical guidelines for the assessment of cognitive behavioural problems in tuberous sclerosis. Eur Child Adolesc Psychiatry 14:183-190.
18. DiMario FJ (2004) Brain abnormalities in tuberous sclerosis complex. J Child Neurol 19:650-657.
19. El-Hashemite N, Zhang H, Henske EP, Kwiatkowski DJ (2003) Mutation in TSC2 activation of mammalian target of rapamycin signalling pathway in renal angiomyolipoma. Lancet 361:1348-1349.
20. Erzurumlu RS, Jhaveri S, Benowitz LI (1990) Transient patterns of GAP-43 expression during the formation of barrels in the rat somatosensory cortex. J Comp Neurol 292:443-456.
21. Ess KC, Uhlmann EJ, Li W, Li H, Declue JE, Crino PB, Gutmann DH (2004) Expression profiling in tuberous sclerosis complex (TSC) knockout mouse astrocytes to characterize human TSC brain pathology. Glia 46:28-40.
22. Ess KC, Kamp CA, Tu BP, Gutmann DH (2005) Developmental origin of subependymal giant cell astrocytoma in tuberous sclerosis complex. Neurology 64:1446-1449.
23. Gomez M, Sampson J, Whittemore V (1999) The tuberous sclerosis complex. Oxford: Oxford UP.
24. Goncharova E, Goncharov D, Noonan D, Krymskaya VP (2004) TSC2 modulates actin cytoskeleton and focal adhesion through TSC1-binding domain and the Rac1 GTPase. J Cell Biol 167:1171-1182.
25. Goncharova EA, Goncharov DA, Eszterhas A, Hunter DS, Glassberg MK, Yeung RS, Walker CL, Noonan D, Kwiatkowski DJ, Chou MM, Panettieri RA, Krymskaya VP (2002) Tuberin regulates p70 S6 kinase activation and ribosomal protein S6 phosphorylation: a role for the TSC2 tumor suppressor gene in pulmonary lymphangioleiomyomatosis (LAM). J Biol Chem 277:30958-30967.
26. Han S, Santos TM, Puga A, Roy J, Thiele EA, McCollin M, Stemmer-Rachamimov A, Ramesh V (2004) Phosphorylation of tuberin as a novel mechanism for somatic inactivation of the tuberous sclerosis complex proteins in brain lesions. Cancer Res 64:812-816.
27. Hirose T, Scheithauer BW, Lopes MB, Gerber HA, Altermatt HJ, Hukee MJ, VandenBerg SR, Charlesworth JC (1995) Tuber and subependymal giant cell astrocytoma associated with tuberous sclerosis: an immunohistochemical, ultrastructural, and immunoelectron and microscopic study. Acta Neuropathol (Berl) 90:387-399.
28. Holz MK, Ballif BA, Gygi SP, Blenis J (2005) mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events. Cell 123:569-580.
29. Hsieh SH, Ferraro GB, Fournier AE (2006) Myelin-associated inhibitors regulate cofilin phosphorylation neuronal inhibition through LIM kinase slingshot phosphatase. J Neurosci 26:1006-1015.
30. Huttenlocher PR, Heydemann PT (1984) Fine structure of cortical tubers in tuberous sclerosis: a Golgi study. Ann Neurol 16:595-602.
31. Inoki K, Corradetti MN, Guan KL (2005) Dysregulation of the TSC-mTOR pathway in human disease. Nat Genet 37:19-24.
32. Ives JR (2005) New chronic EEG electrode for critical/intensive care unit monitoring. J Clin Neurophysiol 22:119-123.
33. Kapfhammer JP, Schwab ME (1994) Inverse patterns of myelination and GAP-43 expression in the adult CNS: neurite growth inhibitors as regulators of neuronal plasticity? J Comp Neurol 340:194-206.
34. Kwiatkowski DJ (2003) Tuberous sclerosis: from tubers to mTOR. Ann Hum Genet 67:87-96.
35. Kwiatkowski DJ, Manning BD (2005) Tuberous sclerosis: a GAP at the crossroads of multiple signaling pathways. Hum Mol Genet 14 [Suppl 2]:R251-R258.
36. Kwiatkowski DJ, Zhang H, Bandura JL, Heiberger KM, Glogauer M, el-Hashemite N, Onda H (2002) A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells. Hum Mol Genet 11:525-534.
37. Lamb RF, Roy C, Diefenbach TJ, Vinters HV, Johnson MW, Jay DG, Hall A (2000) The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho. Nat Cell Biol 2:281-287.
38. Mao X, Fujiwara Y, Orkin SH (1999) Improved reporter strain for monitoring Cre recombinase-mediated DNA excisions in mice. Proc Natl Acad Sci USA 96:5037-5042.
39. Meikle L, McMullen JR, Sherwood MC, Lader AS, Walker V, Chan JA, Kwiatkowski DJ (2005) A mouse model of cardiac rhabdomyoma generated by loss of Tsc1 in ventricular myocytes. Hum Mol Genet 14:429-435.
40. Miyata H, Chiang AC, Vinters HV (2004) Insulin signaling pathways in cortical dysplasia TSC-tubers: tissue microarray analysis. Ann Neurol 56:510-519.
41. Niida Y, Stemmer-Rachamimov AO, Logrip M, Tapon D, Perez R, Kwiatkowski DJ, Sims K, MacCollin M, Louis DN, Ramesh V (2001) Survey of somatic mutations in tuberous sclerosis complex (TSC) hamartomas suggests different genetic mechanisms for pathogenesis of TSC lesions. Am J Hum Genet 69:493-503.
42. Onda H, Crino PB, Zhang H, Murphey RD, Rastelli L, Gould Rothberg BE, Kwiatkowski DJ (2002) Tsc2 null murine neuroepithelial cells are a model for human tuber giant cells, and show activation of an mTOR pathway. Mol Cell Neurosci 21:561-574.
43. Polito A, Reynolds R (2005) NG2-expressing cells as oligodendrocyte progenitors in the normal and demyelinated adult central nervous system. J Anat 207:707-716.
44. Ridler K, Bullmore ET, De Vries PJ, Suckling J, Barker GJ, Meara SJ, Williams SC, Bolton PF (2001) Widespread anatomical abnormalities of grey white matter structure in tuberous sclerosis. Psychol Med 31:1437-1446.
45. Sarbassov DD, Ali SM, Sabatini DM (2005) Growing roles for the mTOR pathway. Curr Opin Cell Biol 17:596-603.
46. Scheithauer BW, Reagan TJ (1999) Neuropathology. In: Tuberous sclerosis complex (Gomez MR, ed) pp 101-144. New York, Oxford UP.
47. Schmued LC, Stowers CC, Scallet AC, Xu L (2005) Fluoro-Jade C results in ultra high resolution contrast labeling of degenerating neurons. Brain Res 1035:24-31.
48. Simons M, Trajkovic K (2006) Neuron-glia communication in the control of oligodendrocyte function and myelin biogenesis. J Cell Sci 119:4381-4389.
49. Talos DM, Fishman RE, Park H, Folkerth RD, Follett PL, Volpe JJ, Jensen FE (2006) Developmental regulation of alpha-amino-3-hydroxy-5-methyl-4- isoxazole-propionic acid receptor subunit expression in forebrain and relationship to regional susceptibility to hypoxic/ischemic injury. I. Rodent cerebral white matter cortex. J Comp Neurol 497:42-60.
50. Tavazoie SF, Alvarez VA, Ridenour DA, Kwiatkowski DJ, Sabatini BL (2005) Regulation of neuronal morphology function by the tumor suppressors Tsc1 and Tsc2. Nat Neurosci 8:1727-1734.
51. Tee AR, Blenis J (2005) mTOR, translational control and human disease. Semin Cell Dev Biol 16:29-37.
52. Thiele EA (2004) Managing epilepsy in tuberous sclerosis complex. J Child Neurol 19:680-686.
53. Tucker T, Friedman JM (2002) Pathogenesis of hereditary tumors: beyond the "two-hit" hypothesis. Clin Genet 62:345-357.
54. Uhlmann EJ, Wong M, Baldwin RL, Bajenaru ML, Onda H, Kwiatkowski DJ, Yamada K, Gutmann DH (2002) Astrocyte-specific TSC1 conditional knockout mice exhibit abnormal neuronal organization and seizures. Ann Neurol 52:285-296.
55. Ulfig N, Nickel J, Bohl J (1998) Monoclonal antibodies SMI 311 and SMI 312 as tools to investigate the maturation of nerve cells and axonal patterns in human fetal brain. Cell Tissue Res 291:433-443.
56. Wang Y, Greenwood JS, Calcagnotto ME, Kirsch HE, Barbaro NM, Baraban SC (2007) Neocortical hyperexcitability in a human case of tuberous sclerosis complex and mice lacking neuronal expression of TSC1. Ann Neurol 61:139-152.
57. Wenzel HJ, Patel LS, Robbins CA, Emmi A, Yeung RS, Schwartzkroin PA (2004) Morphology of cerebral lesions in the Eker rat model of tuberous sclerosis. Acta Neuropathol (Berl) 108:97-108.
58. Wiznitzer M (2004) Autism and tuberous sclerosis. J Child Neurol 19:675-679.
59. Wong M, Ess KC, Uhlmann EJ, Jansen LA, Li W, Crino PB, Mennerick S, Yamada KA, Gutmann DH (2003) Impaired glial glutamate transport in a mouse tuberous sclerosis epilepsy model. Ann Neurol 54:251-256.
60. Wu KY, Hengst U, Cox LJ, Macosko EZ, Jeromin A, Urquhart ER, Jaffrey SR (2005) Local translation of RhoA regulates growth cone collapse. Nature 436:1020-1024.
61. Yeung RS, Katsetos CD, Klein-Szanto A (1997) Subependymal astrocytic hamartomas in the Eker rat model of tuberous sclerosis. Am J Pathol 151:1477-1486.
62. Zhu Y, Romero MI, Ghosh P, Ye Z, Charnay P, Rushing EJ, Marth JD, Parada LF (2001) Ablation of NF1 function in neurons induces abnormal development of cerebral cortex and reactive gliosis in the brain. Genes Dev 15:859-876.
63. Zikou A, Ioannidou MC, Tzoufi M, Astrakas L, Argyropoulou MI (2005) Magnetization transfer ratio measurements of the brain in children with tuberous sclerosis complex. Pediatr Radiol 35:1071-1074.