Nature Genetics
5, 259 - 265 (1993)
doi:10.1038/ng1193-259
Widespread expression of the human and rat Huntington's disease gene in brain and nonneural tissuesTheresa V. Strong1, 2, Danilo A. Tagle1, 2, John M. Valdes3, Lawrence W. Elmer1, 4, Karina Boehm1, Manju Swaroop1, Kevin W. Kaatz4, Francis S. Collins1, 2, 5
& Roger L. Albin4
1Division of Molecular Medicine and Genetics, Department of Internal Medicine, 4570 MSRB II
2Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA
3Cell and Molecular Biology Program, University of Michigan, Ann Arbor, Michigan 48109, USA
4Department of Neurology, Neuroscience Laboratory Building, University of Michigan, 1103 E. Huron, Ann Arbor, Michigan 48104, USA
5National Center for Human Genome Research, NIH, Bethesda, MD 20892, USA Correspondence should be addressed to F.C. We have used RNA in situ hybridization to study the regional expression of the Huntington's disease gene (HD) and its rat homologue in brain and selected nonneural tissues. The HD transcript was expressed throughout the brain in both rat and human, especially in the neurons of the dentate gyrus and pyramidal neurons of the hippocampal formation, cerebellar granule cell layer, cerebellar Purkinje cells and pontine nuclei. Other brain areas expressed lower levels of the HD transcript without pronounced regional differences. Neuronal expression predominated over glial expression in all regions. HD mRNA was also expressed in colon, liver, pancreas and testes. The regional specificity of neuropathology in HD, which is most prominent in the basal ganglia, thus cannot be accounted for by the pattern of expression of HD. REFERENCES
- Folstein, S. In Huntington's Disease: A Disorder of Families (Johns Hopkins, Baltimore, 1989).
- Quarrel, O. & Harper, P.S. In Huntington's Disease (ed. Harper, P.S.) 37−80 (W.B. Saunders, Philadelphia, 1991).
- Morris, M. In Huntington's Disease (ed. Harper, P.S.) 81−126 (W.B. Saunders, Philadelphia, 1991). | ChemPort |
- Quarrel, O. In Huntington's Disease (ed. Harper, P.S.) 141−178 (W.B. Saunders, Philadelphia, 1991).
- Beal, M.F. Does impairment of energy metabolism result in excitoxic neuronal death in neurodegenerative illnesses?. Ann. Neurol. 31, 119−130 (1992). | PubMed | ISI | ChemPort |
- Huntington's Disease Collaborative Research Group. A novel gene contianing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72, 971−983 (1993). | PubMed | ISI |
- DiFiglia, M. Excitotoxic injury of the neostriatum: a model for Huntington's disease. Trends Neurosci. 13, 286−289 (1990). | Article | PubMed | ISI | ChemPort |
- Wexler, N.S. et al. Homozygotes for Huntington's disease. Nature 326, 194−197 (1987). | Article | PubMed | ISI | ChemPort |
- Myers, R.H. et al. Homozygote for Huntington Disease. Am. J. hum. Genet. 45, 615−618 (1989). | PubMed | ISI | ChemPort |
- Sabourin, L.A. et al. Effect of the myotonic dystrophy (DM) mutation on mRNA levels of the DM gene. Nature Genet. 4, 233−238 (1993). | Article | PubMed | ISI | ChemPort |
- Fu, Y.H. et al. Decreased expression of myotonin-protein kinase messenger RNA and protein in adult form of myotonic dystrophy. Science 260, 235−238 (1993). | PubMed | ISI | ChemPort |
- Rosen, D.R. et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362, 59−62 (1993). | Article | PubMed | ISI | ChemPort |
- Ferrante, R.J. et al. Selective sparing of a class of striatal neurons in Huntington's disease. Science 230, 561−563 (1985). | PubMed | ISI | ChemPort |
- Dawbarn, D., DeQuidt, M.E. & Emson, P.C. Survival of basal ganglia neuropeptide Y-somatostatin neurons in Huntington's disease. Brain Res. 340, 251−260 (1985). | Article | PubMed | ISI | ChemPort |
- Ferrante, R.J., Beal, M.F., Kowall, N.W., Richardson, E.P. & Martin, J.B. Sparing of acetylcholinesterase-containing striatal neurons in Huntington's disease. Brain Res. 411, 162−166 (1987). | Article | PubMed | ISI | ChemPort |
- Hirsch, E.C., Graybiel, A.M., Hersh, L.B., Duyckaerts, C. & Agid, Y. Striosomes and extrastriosomal matrix contain different amounts of immunoreactive choline acetyttransferase in the human striatum. Neurosci. Lett. 96, 145−150 (1989). | Article | PubMed | ISI | ChemPort |
- Herrington, K.M. & Kowall, N.W. Parvalbumin immunoreactive neurons resist degeneration in Huntington's disease striatum. J. Neruopath. Exp. Neurol. 50, 309 (1991).
- Reiner, A. et al. Differential loss of striatal projection neurons in Huntington disease. Proc. natn. Acad. Sci. U.S.A. 85, 5733−5737 (1988). | ChemPort |
- Albin, R.L. et al. Abnormalities of striatal projection neurons and N-methyl-D-aspartate receptors in presymptomatic Huntington's disease. New Engl. J. Med. 322, 1293−1298 (1990). | PubMed | ISI | ChemPort |
- Sambrook, J., Fritsch, E.F. & Maniatis, T. In Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory Press, New York, 1989).
- Devereux, J., Haeberli, P. & Smithies, O. A comprehensive set of sequence analysis programs for the VAX. Nucl. Acids Res. 12, 387−395 (1984). | PubMed | ISI | ChemPort |
- Strong, T.V., Boehm, K. & Collins, F.S. Localization of cystic fibrosis transmembrane conductance regulator mRNA in the human gastro-intestinal tract by insitu hybridization. J. clin. Invest. (in the press).
- Paxinos, G. & Watson, C. In The Rat Brain in Stereotaxic Coordinates (Academic Press, Orlando, 1986).
|