{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:59:12Z","timestamp":1790985552084,"version":"4.1.0"},"reference-count":26,"publisher":"The Royal Society","issue":"1386","license":[{"start":{"date-parts":[[1999,6,29]],"date-time":"1999-06-29T00:00:00Z","timestamp":930614400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Phil. Trans. R. Soc. Lond. B"],"published-print":{"date-parts":[[1999,6,29]]},"abstract":"<jats:p>Kennedy'sdisease is an X\u2013linked form of motor neuron disease caused by an expanded polyglutamine repeat in the androgen receptor. While the expansion mutation causes some loss of transcriptional activity by the androgen receptor, the predominant effect of expansion is probably a toxic gain of function, similar to the mechanism of other polyglutamine expansion diseases. Features of the neurodegenerative phenotype of Kennedy'sdisease have now been reproduced in transgenic animals and neuronal cell culture. Nuclear inclusions of mutant androgen receptor protein are found in these model systems and in autopsy samples from patients with Kennedy'sdisease.<\/jats:p>","DOI":"10.1098\/rstb.1999.0461","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T19:55:21Z","timestamp":1027713321000},"page":"1075-1078","source":"Crossref","is-referenced-by-count":33,"title":["Androgen receptor mutation in Kennedy'sdisease"],"prefix":"10.1098","volume":"354","author":[{"given":"Kenneth H.","family":"Fischbeck","sequence":"first","affiliation":[{"name":"Neurogenetics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Lieberman","sequence":"additional","affiliation":[{"name":"Neurogenetics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine K.","family":"Bailey","sequence":"additional","affiliation":[{"name":"Neurology Department, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Abel","sequence":"additional","affiliation":[{"name":"Neurogenetics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane E.","family":"Merry","sequence":"additional","affiliation":[{"name":"Neurology Department, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[1999,6,29]]},"reference":[{"key":"p_1","first-page":"A319","article-title":"Truncated androgen receptor gene with an expanded CAG repeat causes phenotypic changes in transgenic mice (abstract)","volume":"63","author":"Abel A.","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"p_2","doi-asserted-by":"crossref","unstructured":"Bingham P. M. Scott M. O. Wang S. McPhaul M. J. Wilson E. M. Garbern J. Y. Merry D. E. & Fischbeck K. H. 1995 Stability of an expanded trinucleotide repeat in the androgen receptor gene in transgenic mice. Nature Genet. 9 191^196.","DOI":"10.1038\/ng0295-191"},{"key":"p_3","doi-asserted-by":"crossref","unstructured":"Brooks B. P. Paulson H. L. Merry D. E. Salazar-Grueso E. F. Brinkmann A. O. Wilson E. M. & Fischbeck K. H. 1997 Characterization of an expanded glutamine repeat androgen receptor in a neuronal cell culture system. Neurobiol. Dis. 4 313^323.","DOI":"10.1006\/nbdi.1997.0126"},{"key":"p_4","doi-asserted-by":"crossref","DOI":"10.1046\/j.1471-4159.1998.70031054.x","article-title":"A cell culture model for androgen e\u00a1ects in motor neurons","volume":"70","author":"Brooks B. P.","year":"1998","journal-title":"J. Neurochem."},{"key":"p_5","doi-asserted-by":"crossref","unstructured":"Choong C. S. Kemppainen J. A. Zhou Z. & Wilson E. M. 1996 Reduced androgen receptor gene expression with \u00a2rst exon CAG repeat expansion. Mol. Endocrinol. 10 1527^1535.","DOI":"10.1210\/mend.10.12.8961263"},{"key":"p_6","doi-asserted-by":"crossref","unstructured":"Davies S. W. Turmaine M. Cozens B. A. DiFiglia M. Sharp A. H. Ross C. A. Scherzinger E. Wanker E. E. Mangiarini L. & Bates G. P. 1997 Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD muation. Cell 90 537^548.","DOI":"10.1016\/S0092-8674(00)80513-9"},{"key":"p_7","doi-asserted-by":"crossref","unstructured":"DiFiglia M. Sapp E. Chase K. O. Davies S. W. Bates G. P. Vonsattel J. P. & Aronin N. 1997 Aggregation of huntingtin in neuronal inranuclear inclusions and dystrophic neurites in brain. Science 277 1990^1993.","DOI":"10.1126\/science.277.5334.1990"},{"key":"p_8","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0720185.x"},{"key":"p_9","doi-asserted-by":"crossref","unstructured":"Ikeda H. Yamaguchi M. Sugai S. Aze Y. Narumiya S. & Kakizuka A. 1996 Expanded polyglutamine in the Machado Joseph disease protein induces cell death in vitro and in vivo. Nature Genet. 13 196^202.","DOI":"10.1038\/ng0696-196"},{"key":"p_10","doi-asserted-by":"crossref","unstructured":"Kennedy W. R. Alter M. & Sung J. H. 1968 Progressive proximal spinal and bulbar muscuar atrophy of late onset: a sexlinked recessive trait. Neurology 18 671^680.","DOI":"10.1212\/WNL.18.7.671"},{"key":"p_11","doi-asserted-by":"crossref","unstructured":"Kobayashi Y. Miwa S. Merry D. E. Kume A. Mei L. Doyu M. & Sobue G. 1998 Caspase-3 cleaves the expanded androgen receptor protein of spinal and bulbar muscular atrophy in a polyglutamine length-dependent manner. Biochem. Biophys. Res. Comm. 252 145^150.","DOI":"10.1006\/bbrc.1998.9624"},{"key":"p_12","doi-asserted-by":"publisher","DOI":"10.1038\/352077a0"},{"key":"p_13","doi-asserted-by":"crossref","unstructured":"La Spada A. R. Roling D. Harding A. E. Warner C. L. Spiegel R. Hausmanowa-Petrusewicz I. Yee W. C. & Fischbeck K. H. 1992 Meiotic stability and genotype ^ phenotype correlation of the trinucleotide repeat in X-linked spinal and bulbar muscular atrophy. Nature Genet. 2 301^304.","DOI":"10.1038\/ng1292-301"},{"key":"p_14","doi-asserted-by":"crossref","unstructured":"La Spada A. R. (and 13 others) 1998 Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability. Hum. Mol. Genet. 7 959^967.","DOI":"10.1093\/hmg\/7.6.959"},{"key":"p_15","doi-asserted-by":"crossref","unstructured":"Li M. Miwa S. Kobayashi Y. Merry D. E. Yamamoto M. Tanaka F. Doyu M. Hashizume Y. Fischbeck K. H. & Sobue G. 1998a Nuclear inclusions of the androgen receptor protein in spinal and bulbar muscular atrophy. Ann. Neurol. 44 249^254.","DOI":"10.1002\/ana.410440216"},{"key":"p_16","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65612-X"},{"key":"p_17","doi-asserted-by":"crossref","unstructured":"Mangiarini L. (and 10 others) 1996 Exon 1 of the HD gene with an expanded CAG repeat is su\u00a4cient to cause a progressive neurological phenotype in transgenic mice. Cell 87 493^506.","DOI":"10.1016\/S0092-8674(00)81369-0"},{"key":"p_18","first-page":"A469","article-title":"Randomized, double-blind crossover trial of androgen hormone de\u00a2ciency and replacement in X-linked bulbar spinal muscular atrophy (abstract)","volume":"46","author":"Mendell J. R.","year":"1996","journal-title":"Neurology"},{"key":"p_19","first-page":"A271","article-title":"Toward a mouse model for spinal and bulbar muscular atrophy: e\u00a1ect of neuronal expression of androgen receptor in transgenic mice (abstract)","volume":"59","author":"Merry D. E.","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"p_20","doi-asserted-by":"crossref","unstructured":"Merry D. E. Kobayashi Y. Bailey C. K. Taye A. A. & Fischbeck K. H. 1998 Cleavage aggregation and toxicity of the expanded androgen receptor in spinal and bulbar muscular atrophy. Hum. Mol. Genet. 7 693^701.","DOI":"10.1093\/hmg\/7.4.693"},{"key":"p_21","doi-asserted-by":"crossref","unstructured":"Mhatre A. N. Tri\u00a2ro M. A. Kaufman M. Kazemi-Esfarjani P. Figlewicz D. Rouleau G. & Pinsky L. 1993 Reduced transcriptional reglatory competence of the androgen receptor in X-linked spinal and bulbar muscular atrophy. Nature Genet. 5 184^187.","DOI":"10.1038\/ng1093-184"},{"key":"p_22","doi-asserted-by":"crossref","unstructured":"Paulson H. L. Perez M. K. Trottier Y. Trojanowski J. Q. Subramony S. H. Das S. S. Vig P. Mandel J. L. Fischbeck K. H. & Pittman R. N. 1997 Intranuclear inclusions of expanded polylutamine protein in spinocerebellar ataxia type 3. Neuron 19 333^344.","DOI":"10.1016\/S0896-6273(00)80943-5"},{"key":"p_23","first-page":"79","article-title":"Androgen concentration in motor neurons of cranial nerves and spinal cord","volume":"197","author":"Sar M.","year":"1997","journal-title":"Science"},{"key":"p_24","doi-asserted-by":"crossref","unstructured":"Sobue G. Hashizume Y. Mukai E. Hirayama M. Mitsuma T. & Takahashi A. 1989 X-linked recessive bulbospinal neuronopathy. A clinicopathological study. Brain 112 209^232.","DOI":"10.1093\/brain\/112.1.209"},{"key":"p_25","doi-asserted-by":"crossref","unstructured":"Warrick J. M. Paulson H. L. Gray-Board G. L. Bui Q. T. Fischbeck K. H. Pittman R. N. & Bonini N. M. 1998 Expanded polyglutamine protein forms nuclear inclusions and causes neural degeneraion in Drosophila. Cell 93 939^949.","DOI":"10.1016\/S0092-8674(00)81200-3"},{"key":"p_26","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.09-11-03908.1989"}],"container-title":["Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rstb.1999.0461","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rstb.1999.0461","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T21:19:25Z","timestamp":1778620765000},"score":1,"resource":{"primary":{"URL":"http:\/\/royalsocietypublishing.org\/rstb\/article\/354\/1386\/1075-1078\/19468"}},"subtitle":[],"editor":[{"given":"M. F.","family":"Perutz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"P. S.","family":"Harper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"M. A.","family":"Ferguson-Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[1999,6,29]]},"references-count":26,"journal-issue":{"issue":"1386","published-print":{"date-parts":[[1999,6,29]]}},"alternative-id":["10.1098\/rstb.1999.0461"],"URL":"https:\/\/doi.org\/10.1098\/rstb.1999.0461","relation":{},"ISSN":["0962-8436","1471-2970"],"issn-type":[{"value":"0962-8436","type":"print"},{"value":"1471-2970","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,6,29]]}}}