Abstract
Kennedy’s syndrome (X-linked bulbar and spinal muscular atrophy) is an X-linked disorder characterised by sensory and lower motor neurone degeneration.1,2,3 The discovery of a mutation in the androgen receptor (AR) gene in Kennedy’s syndrome reinforced the hypothesis that an X-linked factor might be involved in the disease process of Amyotrophic Lateral Sclerosis (ALS), because of the prevalence of the disease in males, (ratio 1.6:1). This mutation, which is tightly linked with the disease phenotype, consists of an increased number of CAG repeats present in the first exon of the AR gene, encoding a polyglutamine chain.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
La Spada A.R., Wilson E.M., Lubahn D.M., Harding A.E., and Fischbeck K.H. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature. 352:77 (1991).
Harding A.E., Thomas P.K., Baraitser M., Bradbury P.G., Morgan-Hughes J.A., Ponsford J.R. X-linked recessive bulbospinal neuropathy: a report of ten cases. J. Neurol. Neurosurg. Psychiatry 45:1012 (1982).
Sobue G., Hashizume Y., Mukai E., Hirayama M., Mitsuma T., Takahashi A. X-linked recessive bulbospinal neuropathy. Brain. 112:209 (1989).
Sar, M., and Stumpf, W.E. Androgen concentration in motor neurones of cranial nerves and spinal cord. Science. 197:77 (1977).
Simerly, R.B., Chang, C., Muramatsu, M., and Swanson, L.W. Distribution of androgen and oestrogen receptor mRNA-containing cells in the rat brain: an in situ hybridisation study. J. Comp. Nenrol. 294:76 (1990).
Biedler J.L., Helson L., and Spengler B.A. Multiple neurotransmitter synthesis by human neuroblastoma cell lines and clones. Cancer Res. 38:3751 (1973).
Biedler J.L., Helson L., and Spengler B.A. Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in culture. Cancer Res. 33:2643 (1973).
Squinto S.P., Aldrich T.H., Lindsay R.M., Morrissey D.M., Panayotatos N., Bainco S., Furth M.E., and Yancopoulos G. Identification of functional receptoors for ciliary neurotrophic factor on neuronal cell lines and primary culture. Neuron. 5:757 (1990).
Kaplan D.R., Matsumoto K., Lucarelli E., and Thiele C J. Induction of TrkB by retinoic acid mediates biologic responsiveness to BDNF and differentiation of human neuroblastoma cells. Neuron. 11:321 (1993).
Yerramilli-Rao P., Garofalo O., Whatley S., Leigh P.N., and Gallo J.-M. Androgen-controlled specific gene expression in neuroblastoma cells. J. Neurol. Sci. (In Press).
Tilley W.D., Marcelli ML, Wilson J.D., and McPhaul M.J. Characterisation and expression of a cDNA encoding the hAR. Proc. nail. Acad. Sci. U.S.A. 86:327 (1989).
Weiner L.P. Possible role of androgen receptors in Amyotrophic Lateral Sclerosis: a hypothesis. Arch. Neurol. 37:129 (1989).
Kurtzke J.F. Risk factors in Amyotrophic Lateral Sclerosis. In: Rowland L.P., ed. Advances in Neurology. New York: Raven Press, 56:245 (1991).
Brown C.J., Goss S.J., and Lubahn D.B., et al. Induction of the TRPM-2 gene in cells undergoing programmed death. Mol, Cell. Biol. 9:3473 (1989).
Garofalo O., Figlewicz D.A., Leigh P.N., Powell J.F., Meninger V., Dib M., and Rouleau G.A. Androgen receptor gene polymorphisms in amyotrophic lateral sclerosis. Neuromusc. Disord. 3(3): 195 (1993).
Kennedy W.R., Alter M., and Sung J.H. Progressive spinal and bulbar muscular atrophy of late onset: a sex-linked recessive trait. Neurology. 18:671 (1968).
McPhaul M.J., Marcelli M., Tilley W., Griffin J.E., Isidro-Guitierrez R.F., and Wilson J.D. Molecular basis of androgen resistance in a family with a qualitative abnormality of the androgen receptor and responsive to high-dose androgen therapy. J. Clin.Invest. 87:1413 (1991).
Richards R.I., Holman K., Friend K., Kremer E., Hillen D., Staples A., Brown W.T., Goonwardena P., Tarleton J., Schwartz C., et al, Nature Genet. 1:257 (1992).
Mhatre A.N., Trifiro M.A., Kaufman M., Kazemi-Esfarjani P., Figlewicz D., Rouleau G., and Pinsky L. Reduced transcriptional regulatory competence of the androgen receptor in X-linked spinal and bulbar muscular atrophy. Nature Genetics. 5:184 (1993).
Chamberlain N.L., Driver E.D., and Miedfeld R. The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucl. Acids. Res. 22(15):3181 (1994).
Wang Y.-H., Amirhaeri S., Kang S., Wells R.D., and Griffith J.D. Preferential nucleosome assembly at DNA triplet repeats from the Myotonic Dystophy gene. Science. 265:669 (1994).
Toran-Allerand CD. Sex steroids and the development of the newborn mouse hypothalamus and preoptic area in vitro: implications for sexual differentiation. Brain Res. 106:407 (1976).
Jones K.J., and Oblinger M.M. Androgenic regulation of tubulin gene expression in axotomised hamster facial motor neurones. J.Neurosci. 14(6): 3620 (1994).
Katoh-Semba R., Semba R., Kato H., Ueno M., Arakawa Y., and Kato K. Regulation by androgen of levels of the b subunit of NGF and its mRNA in selected regions of the mouse brain. J. Neurochem. 62: 2141 (1994).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Springer Science+Business Media New York
About this chapter
Cite this chapter
Yerramilli-Rao, P.A., Garofalo, O., Leigh, P.N., Gallo, JM. (1996). Effect of the Kennedy Mutation of the Androgen Receptor on Gene Expression in Neuroblastoma Cells. In: Fiskum, G. (eds) Neurodegenerative Diseases. GWUMC Department of Biochemistry and Molecular Biology Annual Spring Symposia. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0209-2_18
Download citation
DOI: https://doi.org/10.1007/978-1-4899-0209-2_18
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4899-0211-5
Online ISBN: 978-1-4899-0209-2
eBook Packages: Springer Book Archive