Graded loss of tuberin in an allelic series of brain models of TSC correlates with survival, and biochemical, histological and behavioral features

Human Molecular Genetics

Volumn 21, Issue 19, 2012, Pages 4286-4300

  Yuan, Elizabeth ^a   Tsai, Peter T ^b   Greene colozzi, Emily ^b   Sahin, Mustafa ^b   Kwiatkowski, David J ^a   Malinowska, Izabela A ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b BOSTON CHILDREN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

SYNAPSIN I; TUBERIN;

ALLELE; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAIN; BRAIN DISEASE; BRAIN NERVE CELL; CELL SURVIVAL; CONTROLLED STUDY; HETEROZYGOSITY; HIPPOCAMPAL CA1 REGION; HIPPOCAMPAL CA3 REGION; HISTOLOGY; HOMOZYGOSITY; IN VIVO STUDY; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; TUBEROUS SCLEROSIS COMPLEX;

ALLELES; ANIMALS; BEHAVIOR; BRAIN; DISEASE MODELS, ANIMAL; FEMALE; HISTOLOGY; HUMANS; MALE; MICE; MICE, KNOCKOUT; SURVIVAL; SYNAPSINS; TUBEROUS SCLEROSIS; TUMOR SUPPRESSOR PROTEINS;

MUS;

EID: 84866354915     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/dds262     Document Type: Article

References (55)

1. Kwiatkowski, D.J., Thiele, E.A. and Whittemore, V.H. (2010) Tuberous Sclerosis Complex. Wiley-VCH, Weinheim, Germany.
2. Thiele, E.A. and Jozwiak, S. (2010) Natural history of tuberous sclerosis complex and overview of manifestations. In Kwiatkowski, D.J., Whittemore, V.H. and Thiele, E.A. (eds.), Tuberous Sclerosis Complex. Wiley-VCH, Weinheim, Germany, pp. 11-20.
3. Winterkorn, E.B., Pulsifer, M.B. and Thiele, E.A. (2007) Cognitive prognosis of patients with tuberous sclerosis complex. Neurology, 68, 62-64.
4. Tierney, K.M., McCartney, D.L., Serfontein, J.R. and De Vries, P.J. (2011) Neuropsychological attention skills and related behaviours in adults with tuberous sclerosis complex. Behav. Genet., 41, 437-444.
5. Yates, J.R., Maclean, C., Higgins, J.N., Humphrey, A., Le Marechal, K., Clifford, M., Carcani-Rathwell, I., Sampson, J.R. and Bolton, P.F. (2011) The Tuberous Sclerosis 2000 Study: presentation, initial assessments and implications for diagnosis and management. Arch. Dis. Child., 96, 1020-1025.
6. Gutierrez, G.C., Smalley, S.L. and Tanguay, P.E. (1998) Autism in tuberous sclerosis complex. J. Autism. Dev. Disord., 28, 97-103.
7. Sampson, J.R., Scahill, S.J., Stephenson, J.B., Mann, L. and Connor, J.M. (1989) Genetic aspects of tuberous sclerosis in the west of Scotland. J. Med. Genet., 26, 28-31.
8. Kwiatkowski, D.J. (2010) Genetics of tuberous sclerosis complex. In Kwiatkowski, D.J., Whittemore, V.H. and Thiele, E.A. (eds), Tuberous Sclerosis Complex: Genes, Clinical Features, and Therapeutics. Wiley-VCH, Winheim, pp. 29-59.
9. Nellist, M., Sancak, O., Goedbloed, M., Adriaans, A., Wessels, M., Maat-Kievit, A., Baars, M., Dommering, C., Van den Ouweland, A. and Halley, D. (2008) Functional characterisation of the TSC1-TSC2 complex to assess multiple TSC2 variants identified in single families affected by tuberous sclerosis complex. BMC Med. Genet., 9, 10.
10. Jansen, A.C., Sancak, O., D'Agostino, M.D., Badhwar, A., Roberts, P., Gobbi, G., Wilkinson, R., Melanson, D., Tampieri, D., Koenekoop, R. et al. (2006) Unusually mild tuberous sclerosis phenotype is associated with TSC2 R905Q mutation. Ann. Neurol., 60, 528-539.
11. O'Connor, S.E., Kwiatkowski, D.J., Roberts, P.S., Wollmann, R.L. and Huttenlocher, P.R. (2003) A family with seizures and minor features of tuberous sclerosis and a novel TSC2 mutation. Neurology, 61, 409-412.
12. Khare, L., Strizheva, G.D., Bailey, J.N., Au, K.S., Northrup, H., Smith, M., Smalley, S.L. and Henske, E.P. (2001) A novel missense mutation in the GTPase activating protein homology region of TSC2 in two large families with tuberous sclerosis complex. J. Med. Genet., 38, 347-349.
13. Wentink, M., Nellist, M., Hoogeveen-Westerveld, M., Zonnenberg, B., Van der Kolk, D., Van Essen, T., Park, S.M., Woods, G., Cohn-Hokke, P., Brussel, W. et al. (2011) Functional characterization of the TSC2 c.3598C.T (p.R1200W) missense mutation that co-segregates with tuberous sclerosis complex in mildly affected kindreds. Clin. Genet., 10.1111/j.1399-0004.2011.01648.x.
14. Yecies, J.L. and Manning, B.D. (2011) mTOR links oncogenic signaling to tumor cell metabolism. J. Mol. Med., 89, 221-228.
15. Zoncu, R., Efeyan, A. and Sabatini, D.M. (2011) mTOR: from growth signal integration to cancer, diabetes and ageing. Nat. Rev. Mol. Cell. Biol., 12, 21-35.
16. Hsu, P.P., Kang, S.A., Rameseder, J., Zhang, Y., Ottina, K.A., Lim, D., Peterson, T.R., Choi, Y., Gray, N.S., Yaffe, M.B. et al. (2011) The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science, 332, 1317-1322.
17. Yu, Y., Yoon, S.O., Poulogiannis, G., Yang, Q., Ma, X.M., Villen, J., Kubica, N., Hoffman, G.R., Cantley, L.C., Gygi, S.P. et al. (2011) Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science, 332, 1322-1326.
18. Tsai, P. and Sahin, M. (2011) Mechanisms of neurocognitive dysfunction and therapeutic considerations in tuberous sclerosis complex. Curr. Opin. Neurol., 24, 106-113.
19. Ehninger, D., Han, S., Shilyansky, C., Zhou, Y., Li, W., Kwiatkowski, D.J., Ramesh, V. and Silva, A.J. (2008) Reversal of learning deficits in a Tsc2(+/2) mouse model of tuberous sclerosis. Nat. Med., 14, 843-848.
20. Goorden, S.M., Van Woerden, G.M., van der Weerd, L., Cheadle, J.P. and Elgersma, Y. (2007) Cognitive deficits in Tsc1+/2 mice in the absence of cerebral lesions and seizures. Ann. Neurol., 62, 648-655.
21. Meikle, L., Talos, D.M., Onda, H., Pollizzi, K., Rotenberg, A., Sahin, M., Jensen, F.E. and Kwiatkowski, D.J. (2007) A mouse model of tuberous sclerosis: neuronal loss of Tsc1 causes dysplastic and ectopic neurons, reduced myelination, seizure activity, and limited survival. J. Neurosci., 27, 5546-5558.
22. Uhlmann, E.J., Wong, M., Baldwin, R.L., Bajenaru, M.L., Onda, H., Kwiatkowski, D.J., Yamada, K. and Gutmann, D.H. (2002) Astrocyte-specific TSC1 conditional knockout mice exhibit abnormal neuronal organization and seizures. Ann. Neurol., 52, 285-296.
23. Way, S.W., McKenna, J. 3rd, Mietzsch, U., Reith, R.M., Wu, H.C. and Gambello, M.J. (2009) Loss of Tsc2 in radial glia models the brain pathology of tuberous sclerosis complex in the mouse. Hum. Mol. Genet., 18, 1252-1265.
24. Pollizzi, K., Malinowska-Kolodziej, I., Doughty, C., Betz, C., Ma, J., Goto, J. and Kwiatkowski, D.J. (2009) A hypomorphic allele of Tsc2 highlights the role of TSC1/TSC2 in signaling to AKT and models mild human TSC2 alleles. Hum. Mol. Genet., 18, 2378-2387.
25. Zhu, Y., Romero, M.I., Ghosh, P., Ye, Z., Charnay, P., Rushing, E.J., Marth, J.D. and Parada, L.F. (2001) Ablation of NF1 function in neurons induces abnormal development of cerebral cortex and reactive gliosis in the brain. Genes Dev., 15, 859-876.
26. Goto, J., Talos, D.M., Klein, P., Qin, W., Chekaluk, Y.I., Anderl, S., Malinowska, I.A., Di Nardo, A., Bronson, R.T., Chan, J.A. et al. (2011) Regulable neural progenitor-specific Tsc1 loss yields giant cells with organellar dysfunction in a model of tuberous sclerosis complex. Proc. Natl. Acad. Sci. USA, 108, E1070-E1079.
27. Tronche, F., Kellendonk, C., Kretz, O., Gass, P., Anlag, K., Orban, P.C., Bock, R., Klein, R. and Schutz, G. (1999) Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat. Genet., 23, 99-103.
28. Anderl, S., Freeland, M., Kwiatkowski, D.J. and Goto, J. (2011) Therapeutic value of prenatal rapamycin treatment in a mouse brain model of tuberous sclerosis complex. Hum. Mol. Genet., 20, 4597-4604.
29. de Vries, P.J., Hunt, A. and Bolton, P.F. (2007) The psychopathologies of children and adolescents with tuberous sclerosis complex (TSC): a postal survey of UK families. Eur. Child. Adolesc. Psychiatry, 16, 16-24.
30. Muzykewicz, D.A., Newberry, P., Danforth, N., Halpern, E.F. and Thiele, E.A. (2007) Psychiatric comorbid conditions in a clinic population of 241 patients with tuberous sclerosis complex. Epilepsy Behav., 11, 506-513.
31. Hogg, S. (1996) A review of the validity and variability of the elevated plus-maze as an animal model of anxiety. Pharmacol. Biochem. Behav., 54, 21-30.
32. Hunt, A. and Shepherd, C. (1993) A prevalence study of autism in tuberous sclerosis. J. Autism Dev. Disord., 23, 323-339.
33. Silverman, J.L., Yang, M., Lord, C. and Crawley, J.N. (2010) Behavioural phenotyping assays for mouse models of autism. Nat. Rev. Neurosci., 11, 490-502.
34. Zeng, L.H., Rensing, N.R., Zhang, B., Gutmann, D.H., Gambello, M.J. and Wong, M. (2011) Tsc2 gene inactivation causes a more severe epilepsy phenotype than Tsc1 inactivation in a mouse model of tuberous sclerosis complex. Hum. Mol. Genet., 20, 445-454.
35. Ferguson, J.N., Young, L.J., Hearn, E.F., Matzuk, M.M., Insel, T.R. and Winslow, J.T. (2000) Social amnesia in mice lacking the oxytocin gene. Nat. Genet., 25, 284-288.
36. Prather, P. and de Vries, P.J. (2004) Behavioral and cognitive aspects of tuberous sclerosis complex. J. Child. Neurol., 19, 666-674.
37. Pulsifer, M.B., Winterkorn, E.B. and Thiele, E.A. (2007) Psychological profile of adults with tuberous sclerosis complex. Epilepsy Behav., 10, 402-406.
38. Young, D.M., Schenk, A.K., Yang, S.B., Jan, Y.N. and Jan, L.Y. (2010) Altered ultrasonic vocalizations in a tuberous sclerosis mouse model of autism. Proc. Natl. Acad. Sci. U S. A., 107, 11074-11079.
39. Numis, A.L., Major, P., Montenegro, M.A., Muzykewicz, D.A., Pulsifer, M.B. and Thiele, E.A. (2011) Identification of risk factors for autism spectrum disorders in tuberous sclerosis complex. Neurology, 76, 981-987.
40. Qin, W., Chan, J.A., Vinters, H.V., Mathern, G.W., Franz, D.N., Taillon, B.E., Bouffard, P. and Kwiatkowski, D.J. (2010) Analysis of TSC cortical tubers by deep sequencing of TSC1, TSC2 and KRAS demonstrates that small second-hit mutations in these genes are rare events. Brain Pathol., 20, 1096-1105.
41. Crino, P.B., Aronica, E., Baltuch, G. and Nathanson, K.L. (2010) Biallelic TSC gene inactivation in tuberous sclerosis complex. Neurology, 74, 1716-1723.
42. Chu-Shore, C.J., Major, P., Camposano, S., Muzykewicz, D. and Thiele, E.A. (2010) The natural history of epilepsy in tuberous sclerosis complex. Epilepsia, 51, 1236-1241.
43. Dabora, S.L., Jozwiak, S., Franz, D.N., Roberts, P.S., Nieto, A., Chung, J., Choy, Y.S., Reeve, M.P., Thiele, E., Egelhoff, J.C. et al. (2001) Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. Am. J. Hum. Genet., 68, 64-80.
44. Van Eeghen, A.M., Black, M.E., Pulsifer, M.B., Kwiatkowski, D.J. and Thiele, E.A. (2012) Genotype and cognitive phenotype of patients with tuberous sclerosis complex. Eur. J. Hum. Genet., 20, 510-5.
45. Verhoef, S., Bakker, L., Tempelaars, A.M., Hesseling-Janssen, A.L., Mazurczak, T., Jozwiak, S., Fois, A., Bartalini, G., Zonnenberg, B.A., van Essen, A.J. et al. (1999) High rate of mosaicism in tuberous sclerosis complex. Am. J. Hum. Genet., 64, 1632-1637.
46. Bissler, J.J., McCormack, F.X., Young, L.R., Elwing, J.M., Chuck, G., Leonard, J.M., Schmithorst, V.J., Laor, T., Brody, A.S., Bean, J. et al. (2008) Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N. Engl. J. Med., 358, 140-151.
47. McCormack, F.X., Inoue, Y., Moss, J., Singer, L.G., Strange, C., Nakata, K., Barker, A.F., Chapman, J.T., Brantly, M.L., Stocks, J.M. et al. (2011) Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N. Engl. J. Med., 364, 1595-1606.
48. Krueger, D.A., Care, M.M., Holland, K., Agricola, K., Tudor, C., Mangeshkar, P., Wilson, K.A., Byars, A., Sahmoud, T. and Franz, D.N. (2010) Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N. Engl. J. Med., 363, 1801-1811.
49. Onda, H., Lueck, A., Marks, P.W., Warren, H.B. and Kwiatkowski, D.J. (1999) Tsc2(+/2) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background. J. Clin. Invest., 104, 687-695.
50. Soriano, P. (1999) Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat. Genet., 21, 70-71.
51. Meikle, L., McMullen, J.R., Sherwood, M.C., Lader, A.S., Walker, V., Chan, J.A. and Kwiatkowski, D.J. (2005) A mouse model of cardiac rhabdomyoma generated by loss of Tsc1 in ventricular myocytes. Hum. Mol. Genet., 14, 429-435.
52. Kozlowski, P., Roberts, P., Dabora, S., Franz, D., Bissler, J., Northrup, H., Au, K.S., Lazarus, R., Domanska-Pakiela, D., Kotulska, K. et al. (2007) Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations. Hum. Genet., 121, 389-400.
53. Bednar, I., Paterson, D., Marutle, A., Pham, T.M., Svedberg, M., Hellstrom-Lindahl, E., Mousavi, M., Court, J., Morris, C., Perry, E. et al. (2002) Selective nicotinic receptor consequences in APP(SWE) transgenic mice. Mol. Cell. Neurosci., 20, 354-365.
54. Holmes, A., Wrenn, C.C., Harris, A.P., Thayer, K.E. and Crawley, J.N. (2002) Behavioral profiles of inbred strains on novel olfactory, spatial and emotional tests for reference memory in mice. Genes Brain Behav., 1, 55-69.
55. Buitrago, M.M., Schulz, J.B., Dichgans, J. and Luft, A.R. (2004) Short and long-term motor skill learning in an accelerated rotarod training paradigm. Neurobiol. Learn. Mem., 81, 211-216.