Silencing neuronal mutant androgen receptor in a mouse model of spinal and bulbar muscular atrophy

Human Molecular Genetics

Volumn 24, Issue 21, 2015, Pages 5985-5994

  Sahashi, Kentaro ^a   Katsuno, Masahisa ^a   Hung, Gene ^b   Adachi, Hiroaki ^c   Kondo, Naohide ^a   Nakatsuji, Hideaki ^a   Tohnai, Genki ^a   Iida, Madoka ^a   Bennett, Frank ^b   Sobue, Gen ^a  

^a NAGOYA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^b ISIS PHARMACEUTICALS   (United States)

^c UNIVERSITY OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN RECEPTOR; ANTISENSE OLIGONUCLEOTIDE; RNA; AR PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CAG REPEAT; CONTROLLED STUDY; DOSE RESPONSE; DRUG EFFECT; DRUG TARGETING; FEMALE; GENE EXPRESSION; GENE SILENCING; HISTOPATHOLOGY; KENNEDY DISEASE; MOTONEURON; MOTOR DYSFUNCTION; MOTOR UNIT; MOUSE; NERVE CELL DEGENERATION; NEUROMUSCULAR SYNAPSE; NEUROTOXICITY; NONHUMAN; PATHOGENESIS; PHENOTYPE; PRIORITY JOURNAL; SKELETAL MUSCLE; SURVIVAL; WEIGHT GAIN; ANIMAL; DISEASE COURSE; DRUG EFFECTS; GENETICS; MUSCULAR ATROPHY, SPINAL; MUTATION; NEUROMUSCULAR JUNCTION; PATHOLOGY; TRANSGENIC MOUSE;

ANIMALS; DISEASE PROGRESSION; GENE EXPRESSION; GENE SILENCING; MICE; MICE, TRANSGENIC; MOTOR NEURONS; MUSCLE, SKELETAL; MUSCULAR ATROPHY, SPINAL; MUTATION; NEUROMUSCULAR JUNCTION; OLIGONUCLEOTIDES, ANTISENSE; RECEPTORS, ANDROGEN;

EID: 84949236211     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddv300     Document Type: Article

References (47)

1. Sambataro, F. and Pennuto, M. (2012) Cell-autonomous and non-cell-autonomous toxicity in polyglutamine diseases. Prog. Neurobiol., 97, 152-172.
2. Orsucci, D., Rocchi, A., Caldarazzo Ienco, E., Ali, G., LoGerfo, A., Petrozzi, L., Scarpelli, M., Filosto, M., Carlesi, C., Siciliano, G. et al. (2014) Myopathic involvement and mitochondrial pathology in Kennedy disease and in other motor neuron diseases. Curr. Mol. Med., 14, 598-602.
3. Katsuno, M., Adachi, H., Minamiyama, M., Waza, M., Tokui, K., Banno, H., Suzuki, K., Onoda, Y., Tanaka, F., Doyu, M. et al. (2006) Reversible disruption of dynactin 1-mediated retrograde axonal transport in polyglutamine-induced motor neuron degeneration. J. Neurosci., 26, 12106-12117.
4. Ranganathan, S., Harmison, G.G., Meyertholen, K., Pennuto, M., Burnett, B.G. and Fischbeck, K.H. (2009) Mitochondrial abnormalities in spinal and bulbar muscular atrophy. Hum. Mol. Genet., 18, 27-42.
5. Kemp, M.Q., Poort, J.L., Baqri, R.M., Lieberman, A.P., Breedlove, S.M., Miller, K.E. and Jordan, C.L. (2011) Impaired motoneuronal retrograde transport in two models of SBMA implicates two sites of androgen action. Hum. Mol. Genet., 20, 4475-4490.
6. Minamiyama, M., Katsuno, M., Adachi, H., Doi, H., Kondo, N., Iida, M., Ishigaki, S., Fujioka, Y., Matsumoto, S., Miyazaki, Y. et al. (2012) Naratriptan mitigates CGRP1-associated motor neuron degeneration caused by an expanded polyglutamine repeat tract. Nat. Med., 18, 1531-1538.
7. Iida, M., Katsuno, M., Nakatsuji, H., Adachi, H., Kondo, N., Miyazaki, Y., Tohnai, G., Ikenaka, K., Watanabe, H., Yamamoto, M. et al. (2015) Pioglitazone suppresses neuronal and muscular degeneration caused by polyglutamine-expanded androgen receptors. Hum. Mol. Genet., 24, 314-329.
8. Nedelsky, N.B., Pennuto, M., Smith, R.B., Palazzolo, I., Moore, J., Nie, Z., Neale, G. and Taylor, J.P. (2010) Native functions of the androgen receptor are essential to pathogenesis in a Drosophila model of spinobulbar muscular atrophy. Neuron, 67, 936-952.
9. Orr, C.R., Montie, H.L., Liu, Y., Bolzoni, E., Jenkins, S.C., Wilson, E.M., Joseph, J.D., McDonnell, D.P. and Merry, D.E. (2010) An interdomain interaction of the androgen receptor is required for its aggregation and toxicity in spinal and bulbar muscular atrophy. J. Biol. Chem., 285, 35567-35577.
10. Katsuno, M., Tanaka, F., Adachi, H., Banno, H., Suzuki, K., Watanabe, H. and Sobue, G. (2012) Pathogenesis and therapy of spinal and bulbar muscular atrophy (SBMA). Prog. Neurobiol., 99, 246-256.
11. Li, M., Nakagomi, Y., Kobayashi, Y., Merry, D.E., Tanaka, F., Doyu, M., Mitsuma, T., Hashizume, Y., Fischbeck, K.H. and Sobue, G. (1998) Nonneural nuclear inclusions of androgen receptor protein in spinal and bulbar muscular atrophy. Am. J. Pathol., 153, 695-701.
12. Adachi, H., Katsuno, M., Minamiyama, M., Waza, M., Sang, C., Nakagomi, Y., Kobayashi, Y., Tanaka, F., Doyu, M., Inukai, A. et al. (2005) Widespread nuclear and cytoplasmic accumulation of mutant androgen receptor in SBMA patients. Brain, 128, 659-670.
13. Boyer, J.G., Ferrier, A. and Kothary, R. (2013) More than a bystander: the contributions of intrinsic skeletal muscle defects in motor neuron diseases. Front. Physiol., 4, 356.
14. Funakoshi, H., Belluardo, N., Arenas, E., Yamamoto, Y., Casabona, A., Persson, H. and Ibanez, C.F. (1995) Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons. Science, 268, 1495-1499.
15. Soraru, G., D'Ascenzo, C., Polo, A., Palmieri, A., Baggio, L., Vergani, L., Gellera, C., Moretto, G., Pegoraro, E. and Angelini, C. (2008) Spinal and bulbar muscular atrophy: skeletal muscle pathology in male patients and heterozygous females. J. Neurol. Sci., 264, 100-105.
16. Rinaldi, C., Bott, L.C., Chen, K.L., Harmison, G.G., Katsuno, M., Sobue, G., Pennuto, M. and Fischbeck, K.H. (2012) Insulin-like growth factor (IGF)-1 administration ameliorates disease manifestations in a mouse model of spinal and bulbar muscular atrophy. Mol. Med., 18, 1261-1268.
17. Monks, D.A., Johansen, J.A., Mo, K., Rao, P., Eagleson, B., Yu, Z., Lieberman, A.P., Breedlove, S.M. and Jordan, C.L. (2007) Overexpression of wild-type androgen receptor in muscle recapitulates polyglutamine disease. Proc. Natl. Acad. Sci. USA, 104, 18259-18264.
18. Cortes, C.J., Ling, S.C., Guo, L.T., Hung, G., Tsunemi, T., Ly, L., Tokunaga, S., Lopez, E., Sopher, B.L., Bennett, C.F. et al. (2014) Muscle expression of mutant androgen receptor accounts for systemic and motor neuron disease phenotypes in spinal and bulbar muscular atrophy. Neuron, 82, 295-307.
19. Lieberman, A.P., Yu, Z., Murray, S., Peralta, R., Low, A., Guo, S., Yu, X.X., Cortes, C.J., Bennett, C.F., Monia, B.P. et al. (2014) Peripheral androgen receptor gene suppression rescues disease in mouse models of spinal and bulbar muscular atrophy. Cell Rep., 7, 774-784.
20. Sobue, G., Hashizume, Y., Mukai, E., Hirayama, M., Mitsuma, T. and Takahashi, A. (1989) X-linked recessive bulbospinal neuronopathy. A clinicopathological study. Brain, 112(Pt 1), 209-232.
21. Sobue, G., Doyu, M., Kachi, T., Yasuda, T., Mukai, E., Kumagai, T. and Mitsuma, T. (1993) Subclinical phenotypic expressions in heterozygous females of X-linked recessive bulbospinal neuronopathy. J. Neurol. Sci., 117, 74-78.
22. Li, M., Sobue, G., Doyu, M., Mukai, E., Hashizume, Y. and Mitsuma, T. (1995) Primary sensory neurons in X-linked recessive bulbospinal neuropathy: histopathology and androgen receptor gene expression. Muscle Nerve, 18, 301-308.
23. Lehky, T.J., Chen, C.J., di Prospero, N.A., Rhodes, L.E., Fischbeck, K. and Floeter, M.K. (2009) Standard and modified statistical MUNE evaluations in spinal-bulbar muscular atrophy. Muscle Nerve, 40, 809-814.
24. Suzuki, K., Katsuno, M., Banno, H., Takeuchi, Y., Kawashima, M., Suga, N., Hashizume, A., Hama, T., Uchida, K., Yamashita, F. et al. (2010) The profile of motor unit number estimation (MUNE) in spinal and bulbar muscular atrophy. J. Neurol. Neurosurg. Psychiatry, 81, 567-571.
25. Grunseich, C., Kats, I.R., Bott, L.C., Rinaldi, C., Kokkinis, A., Fox, D., Chen, K.L., Schindler, A.B., Mankodi, A.K., Shrader, J.A. et al. (2014) Early onset and novel features in a spinal and bulbar muscular atrophy patient with a 68 CAG repeat. Neuromuscul. Disord., 35, 978-981.
26. Katsuno, M., Adachi, H., Kume, A., Li, M., Nakagomi, Y., Niwa, H., Sang, C., Kobayashi, Y., Doyu, M. and Sobue, G. (2002) Testosterone reduction prevents phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Neuron, 35, 843-854.
27. Kondo, N., Katsuno, M., Adachi, H., Minamiyama, M., Doi, H., Matsumoto, S., Miyazaki, Y., Iida, M., Tohnai, G., Nakatsuji, H. et al. (2013) Heat shock factor-1 influences pathological lesion distribution of polyglutamine-induced neurodegeneration. Nat. Commun., 4, 1405.
28. Crooke, S.T. (2007) Antisense Drug Technology: Principles, Strategies, and Applications, 2nd edn, CRC Press, Boca Raton, FL.
29. Sahashi, K., Hua, Y., Ling, K.K., Hung, G., Rigo, F., Horev, G., Katsuno, M., Sobue, G., Ko, C.P., Bennett, C.F. et al. (2012) TSUNAMI: an antisense method to phenocopy splicing-associated diseases in animals. Genes Dev., 26, 1874-1884.
30. Sahashi, K., Ling, K.K., Hua, Y., Wilkinson, J.E., Nomakuchi, T., Rigo, F., Hung, G., Xu, D., Jiang, Y.P., Lin, R.Z. et al. (2013) Pathological impact of SMN2 mis-splicing in adult SMA mice. EMBO Mol. Med., 5, 1586-1601.
31. Thomas, P.S. Jr, Fraley, G.S., Damian, V., Woodke, L.B., Zapata, F., Sopher, B.L., Plymate, S.R. and La Spada, A.R. (2006) Loss of endogenous androgen receptor protein accelerates motor neuron degeneration and accentuates androgen insensitivity in a mouse model of X-linked spinal and bulbar muscular atrophy. Hum. Mol. Genet., 15, 2225-2238.
32. Bennett, C.F. and Swayze, E.E. (2010) RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu. Rev. Pharmacol. Toxicol., 50, 259-293.
33. Yang, Z.F., Ho, D.W., Lau, C.K., Lam, C.T., Lum, C.T., Poon, R.T. and Fan, S.T. (2005) Allograft inflammatory factor-1 (AIF-1) is crucial for the survival and pro-inflammatory activity of macrophages. Int. Immunol., 17, 1391-1397.
34. Hua, Y., Sahashi, K., Hung, G., Rigo, F., Passini, M.A., Bennett, C.F. and Krainer, A.R. (2010) Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model. Genes Dev., 24, 1634-1644.
35. Dubowitz, V. and Sewry, C.A. (2007) Muscle Biopsy: A Practical Approach, 3rd edn, Elsevier, Amsterdam, Netherlands.
36. Moresi, V., Williams, A.H., Meadows, E., Flynn, J.M., Potthoff, M.J., McAnally, J., Shelton, J.M., Backs, J., Klein, W.H., Richardson, J.A. et al. (2010) Myogenin and class II HDACs control neurogenic muscle atrophy by inducing E3 ubiquitin ligases. Cell, 143, 35-45.
37. Manzano, R., Toivonen, J.M., Olivan, S., Calvo, A.C., Moreno-Igoa, M., Munoz, M.J., Zaragoza, P., Garcia-Redondo, A. and Osta, R. (2011) Altered expression of myogenic regulatory factors in the mouse model of amyotrophic lateral sclerosis. Neurodegener. Dis., 8, 386-396.
38. Calvo, A.C., Manzano, R., Atencia-Cibreiro, G., Olivan, S., Munoz, M.J., Zaragoza, P., Cordero-Vazquez, P., Esteban-Perez, J., Garcia-Redondo, A. and Osta, R. (2012) Genetic biomarkers for ALS disease in transgenic SOD1(G93A) mice. PLoS ONE, 7, e32632.
39. Rudolf, R., Khan, M.M., Labeit, S. and Deschenes, M.R. (2014) Degeneration of neuromuscular junction in age and dystrophy. Front. Aging Neurosci., 6, 99.
40. Smith, R.A., Miller, T.M., Yamanaka, K., Monia, B.P., Condon, T.P., Hung, G., Lobsiger, C.S., Ward, C.M., McAlonis-Downes, M., Wei, H. et al. (2006) Antisense oligonucleotide therapy for neurodegenerative disease. J. Clin. Invest., 116, 2290-2296.
41. Passini, M.A., Bu, J., Richards, A.M., Kinnecom, C., Sardi, S.P., Stanek, L.M., Hua, Y., Rigo, F., Matson, J., Hung, G. et al. (2011) Antisense oligonucleotides delivered to the mouse CNS ameliorate symptoms of severe spinal muscular atrophy. Sci. Transl. Med., 3, 72ra18.
42. Raskin, K., de Gendt, K., Duittoz, A., Liere, P., Verhoeven, G., Tronche, F. and Mhaouty-Kodja, S. (2009) Conditional inactivation of androgen receptor gene in the nervous system: effects on male behavioral and neuroendocrine responses. J. Neurosci., 29, 4461-4470.
43. Yu, I.C., Lin, H.Y., Liu, N.C., Sparks, J.D., Yeh, S., Fang, L.Y., Chen, L. and Chang, C. (2013) Neuronal androgen receptor regulates insulin sensitivity via suppression of hypothalamic NF-kappaB-mediated PTP1B expression. Diabetes, 62, 411-423.
44. Hua, Y., Sahashi, K., Rigo, F., Hung, G., Horev, G., Bennett, C.F. and Krainer, A.R. (2011) Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model. Nature, 478, 123-126.
45. Hua, Y., Liu, Y.H., Sahashi, K., Rigo, F., Bennett, C.F. and Krainer, A.R. (2015) Motor neuron cell-nonautonomous rescue of spinal muscular atrophy phenotypes in mild and severe transgenic mouse models. Genes Dev., 29, 288-297.
46. Miller, T.M., Pestronk, A., David, W., Rothstein, J., Simpson, E., Appel, S.H., Andres, P.L., Mahoney, K., Allred, P., Alexander, K. et al. (2013) An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. Lancet Neurol., 12, 435-442.
47. Katsuno, M., Adachi, H., Minamiyama, M., Waza, M., Doi, H., Kondo, N., Mizoguchi, H., Nitta, A., Yamada, K., Banno, H. et al. (2010) Disrupted transforming growth factor-beta signaling in spinal and bulbar muscular atrophy. J. Neurosci., 30, 5702-5712.