Specific correction of a splice defect in brain by nutritional supplementation

Human Molecular Genetics

Volumn 20, Issue 21, 2011, Pages 4093-4101

  Shetty, Ranjit S ^a   Gallagher, Cary S ^a   Chen, Yei Tsung ^a   Hims, Matthew M ^a   Mull, James ^a   Leyne, Maire ^a   Pickel, James ^b   Kwok, David ^c   Slaugenhaupt, Susan A ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

^c BRI Biopharmaceutical Research Inc   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

KINETIN; MESSENGER RNA; PROTEIN; PROTEIN IKAP; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BACTERIAL ARTIFICIAL CHROMOSOME; BRAIN DISEASE; CONTROLLED STUDY; DIET SUPPLEMENTATION; DYSAUTONOMIA; EMBRYO; FEMALE; GENE MUTATION; GENETIC DISORDER; MALE; MOUSE; NERVE CELL CULTURE; NONHUMAN; PRIORITY JOURNAL; RNA ANALYSIS; RNA SPLICING; TRANSGENIC MOUSE;

ALTERNATIVE SPLICING; ANIMALS; BRAIN; CARRIER PROTEINS; CELLS, CULTURED; DIET; DIETARY SUPPLEMENTS; DOSE-RESPONSE RELATIONSHIP, DRUG; KINETIN; MICE; MICE, TRANSGENIC; NEURONS;

BACTERIA (MICROORGANISMS); MUS; MUS MUSCULUS;

EID: 80053967115     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddr333     Document Type: Article

References (46)

1. Blencowe, B.J. (2006) Alternative splicing: new insights from global analyses. Cell, 126, 37-47.
2. Johnson, J.M., Castle, J., Garrett-Engele, P., Kan, Z., Loerch, P.M., Armour, C.D., Santos, R., Schadt, E.E., Stoughton, R. and Shoemaker, D.D. (2003) Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science, 302, 2141-2144.
3. Modrek, B. and Lee, C. (2002) A genomic view of alternative splicing. Nat. Genet., 30, 13-19.
4. Cartegni, L., Chew, S.L. and Krainer, A.R. (2002) Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat. Rev. Genet., 3, 285-298.
5. Faustino, N.A. and Cooper, T.A. (2003) Pre-mRNA splicing and human disease. Genes Dev., 17, 419-437.
6. Beck, S., Penque, D., Garcia, S., Gomes, A., Farinha, C., Mata, L., Gulbenkian, S., Gil-Ferreira, K., Duarte, A., Pacheco, P. et al. (1999) Cystic fibrosis patients with the 3272-26A→G mutation have mild disease, leaky alternative mRNA splicing, and CFTR protein at the cell membrane. Hum. Mutat., 14, 133-144.
7. Svenson, I.K., Ashley-Koch, A.E., Gaskell, P.C., Riney, T.J., Cumming, W.J., Kingston, H.M., Hogan, E.L., Boustany, R.M., Vance, J.M., Nance, M.A. et al. (2001) Identification and expression analysis of spastin gene mutations in hereditary spastic paraplegia. Am. J. Hum. Genet., 68, 1077-1085.
8. Nissim-Rafinia, M. and Kerem, B. (2005) The splicing machinery is a genetic modifier of disease severity. Trends Genet., 21, 480-483.
9. Moller, L.B., Tumer, Z., Lund, C., Petersen, C., Cole, T., Hanusch, R., Seidel, J., Jensen, L.R. and Horn, N. (2000) Similar splice-site mutations of the ATP7A gene lead to different phenotypes: classical Menkes disease or occipital horn syndrome. Am. J. Hum. Genet., 66, 1211-1220.
10. Garcia-Blanco, M.A., Baraniak, A.P. and Lasda, E.L. (2004) Alternative splicing in disease and therapy. Nat. Biotechnol., 22, 535-546.
11. Yeo, G.W. (2005) Splicing regulators: targets and drugs. Genome Biol., 6, 240.
12. Axelrod, F.B. (2004) Familial dysautonomia. Muscle Nerve, 29, 352-363.
13. Lehavi, O., Aizenstein, O., Bercovich, D., Pavzner, D., Shomrat, R., Orr-Urtreger, A. and Yaron, Y. (2003) Screening for familial dysautonomia in Israel: evidence for higher carrier rate among Polish Ashkenazi Jews. Genet. Test., 7, 139-142.
14. Maayan, C., Kaplan, E., Shachar, S., Peleg, O. and Godfrey, S. (1987) Incidence of familial dysautonomia in Israel 1977-1981. Clin. Genet., 32, 106-108.
15. Gold-von Simson, G. and Axelrod, F.B. (2006) Familial dysautonomia: update and recent advances. Curr. Probl. Pediatr. Adolesc. Health Care, 36, 218-237.
16. Ngai, J., Kreynin, I., Kim, J.T. and Axelrod, F.B. (2006) Anesthesia management of familial dysautonomia. Paediatr. Anaesth., 16, 611-620.
17. Anderson, S.L., Coli, R., Daly, I.W., Kichula, E.A., Rork, M.J., Volpi, S.A., Ekstein, J. and Rubin, B.Y. (2001) Familial dysautonomia is caused by mutations of the IKAP gene. Am. J. Hum. Genet., 68, 753-758.
18. Slaugenhaupt, S.A., Blumenfeld, A., Gill, S.P., Leyne, M., Mull, J., Cuajungco, M.P., Liebert, C.B., Chadwick, B., Idelson, M., Reznik, L. et al. (2001) Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia. Am. J. Hum. Genet., 68, 598-605.
19. Leyne, M., Mull, J., Gill, S.P., Cuajungco, M.P., Oddoux, C., Blumenfeld, A., Maayan, C., Gusella, J.F., Axelrod, F.B. and Slaugenhaupt, S.A. (2003) Identification of the first non-Jewish mutation in familial Dysautonomia. Am. J. Med. Genet. A, 118A, 305-308.
20. Ibrahim, E.C., Hims, M.M., Shomron, N., Burge, C.B., Slaugenhaupt, S.A. and Reed, R. (2007) Weak definition of IKBKAP exon 20 leads to aberrant splicing in familial dysautonomia. Hum. Mutat., 28, 41-53.
21. Cuajungco, M.P., Leyne, M., Mull, J., Gill, S.P., Lu, W., Zagzag, D., Axelrod, F.B., Maayan, C., Gusella, J.F. and Slaugenhaupt, S.A. (2003) Tissue-specific reduction in splicing efficiency of IKBKAP due to the major mutation associated with familial dysautonomia. Am. J. Hum. Genet., 72, 749-758.
22. Cohen, L., Henzel, W.J. and Baeuerle, P.A. (1998) IKAP is a scaffold protein of the IkappaB kinase complex. Nature, 395, 292-296.
23. Krappmann, D., Hatada, E.N., Tegethoff, S., Li, J., Klippel, A., Giese, K., Baeuerle, P.A. and Scheidereit, C. (2000) The I kappa B kinase (IKK) complex is tripartite and contains IKK gamma but not IKAP as a regular component. J. Biol. Chem., 275, 29779-29787.
24. Hawkes, N.A., Otero, G., Winkler, G.S., Marshall, N., Dahmus, M.E., Krappmann, D., Scheidereit, C., Thomas, C.L., Schiavo, G., Erdjument-Bromage, H. et al. (2002) Purification and characterization of the human elongator complex. J. Biol. Chem., 277, 3047-3052.
25. Otero, G., Fellows, J., Li, Y., de Bizemont, T., Dirac, A.M., Gustafsson, C.M., Erdjument-Bromage, H., Tempst, P. and Svejstrup, J.Q. (1999) Elongator, a multisubunit component of a novel RNA polymerase II holoenzyme for transcriptional elongation. Mol. Cell, 3, 109-118.
26. Svejstrup, J.Q. (2007) Elongator complex: how many roles does it play? Curr. Opin. Cell Biol., 19, 331-336.
27. Esberg, A., Huang, B., Johansson, M.J. and Bystrom, A.S. (2006) Elevated levels of two tRNA species bypass the requirement for elongator complex in transcription and exocytosis. Mol. Cell, 24, 139-148.
28. Holmberg, C., Katz, S., Lerdrup, M., Herdegen, T., Jaattela, M., Aronheim, A. and Kallunki, T. (2002) A novel specific role for I kappa B kinase complex-associated protein in cytosolic stress signaling. J. Biol. Chem., 277, 31918-31928.
29. Rahl, P.B., Chen, C.Z. and Collins, R.N. (2005) Elp1p, the yeast homolog of the FD disease syndrome protein, negatively regulates exocytosis independently of transcriptional elongation. Mol. Cell, 17, 841-853.
30. Cheishvili, D., Maayan, C., Smith, Y., Ast, G. and Razin, A. (2007) IKAP/ hELP1 deficiency in the cerebrum of familial dysautonomia patients results in down regulation of genes involved in oligodendrocyte differentiation and in myelination. Hum. Mol. Genet., 16, 2097-2104.
31. Close, P., Hawkes, N., Cornez, I., Creppe, C., Lambert, C.A., Rogister, B., Siebenlist, U., Merville, M.P., Slaugenhaupt, S.A., Bours, V. et al. (2006) Transcription impairment and cell migration defects in elongator-depleted cells: implication for familial dysautonomia. Mol. Cell, 22, 521-531.
32. Chen, Y.T., Hims, M.M., Shetty, R.S., Mull, J., Liu, L., Leyne, M. and Slaugenhaupt, S.A. (2009) Loss of mouse Ikbkap, a subunit of elongator, leads to transcriptional deficits and embryonic lethality that can be rescued by human IKBKAP. Mol. Cell. Biol., 29, 736-744.
33. Slaugenhaupt, S.A., Mull, J., Leyne, M., Cuajungco, M.P., Gill, S.P., Hims, M.M., Quintero, F., Axelrod, F.B. and Gusella, J.F. (2004) Rescue of a human mRNA splicing defect by the plant cytokinin kinetin. Hum. Mol. Genet., 13, 429-436.
34. Hims, M.M., Ibrahim, E.C., Leyne, M., Mull, J., Liu, L., Lazaro, C., Shetty, R.S., Gill, S., Gusella, J.F., Reed, R. et al. (2007) Therapeutic potential and mechanism of kinetin as a treatment for the human splicing disease familial dysautonomia. J. Mol. Med., 85, 149-161.
35. Pros, E., Fernandez-Rodriguez, J., Benito, L., Ravella, A., Capella, G., Blanco, I., Serra, E. and Lazaro, C. (2009) Modulation of aberrant NF1 pre-mRNA splicing by kinetin treatment. Eur. J. Hum. Genet., 18, 614-617.
36. Hims, M.M., Shetty, R.S., Pickel, J., Mull, J., Leyne, M., Liu, L., Gusella, J.F. and Slaugenhaupt, S.A. (2007) A humanized IKBKAP transgenic mouse models a tissue-specific human splicing defect. Genomics, 90, 389-396.
37. Gold-von Simson, G., Goldberg, J.D., Rolnitzky, L.M., Mull, J., Leyne, M., Voustianiouk, A., Slaugenhaupt, S.A. and Axelrod, F.B. (2009) Kinetin in familial dysautonomia carriers: implications for a new therapeutic strategy targeting mRNA splicing. Pediatr. Res., 65, 341-346.
38. Byers, P.H. (2002) Killing the messenger: new insights into nonsense-mediated mRNA decay. J. Clin. Invest., 109, 3-6.
39. Anderson, S.L., Qiu, J. and Rubin, B.Y. (2003) EGCG corrects aberrant splicing of IKAP mRNA in cells from patients with familial dysautonomia. Biochem. Biophys. Res. Commun., 310, 627-633.
40. Anderson, S.L., Qiu, J. and Rubin, B.Y. (2003) Tocotrienols induce IKBKAP expression: a possible therapy for familial dysautonomia. Biochem. Biophys. Res. Commun., 306, 303-309.
41. Keren, H., Donyo, M., Zeevi, D., Maayan, C., Pupko, T. and Ast, G. (2010) Phosphatidylserine increases IKBKAP levels in familial dysautonomia cells. PLoS One, 5, e15884.
42. Lee, G., Papapetrou, E.P., Kim, H., Chambers, S.M., Tomishima, M.J., Fasano, C.A., Ganat, Y.M., Menon, J., Shimizu, F., Viale, A. et al. (2009) Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature, 461, 402-406.
43. Gold-von Simson, G., Leyne, M., Mull, J., Rolnitzky, L.M., Goldberg, J.D., Berlin, D., Axelrod, F.B. and Slaugenhaupt, S.A. (2008) IKBKAP mRNA in peripheral blood leukocytes: a molecular marker of gene expression and splicing in familial dysautonomia. Pediatr. Res., 63, 186-190.
44. Boone, N., Loriod, B., Bergon, A., Sbai, O., Formisano-Treziny, C., Gabert, J., Khrestchatisky, M., Nguyen, C., Feron, F., Axelrod, F.B. et al. (2010) Olfactory stem cells, a new cellular model for studying molecular mechanisms underlying familial dysautonomia. PLoS One, 5, e15590.
45. Lesuisse, C. and Martin, L.J. (2002) Immature and mature cortical neurons engage different apoptotic mechanisms involving caspase-3 and the mitogen-activated protein kinase pathway. J. Cereb. Blood Flow Metab., 22, 935-950.
46. Reis, S.A., Oostra, B.A. and Willemsen, R. (2006) Isolation of mouse neuritic mRNAs. J. Mol. Histol., 37, 79-86.