Abstract
The incurable neurodegenerative disorder, Huntington's disease (HD), is caused by an expanded, unstable CAG repeat encoding a stretch of polyglutamine in a 4p16.3 gene (HD) of unknown function. Near the CAG repeat is a polyproline-encoding CCG repeat that shows more limited allelic variation. The mouse homologue,Hdh, has been mapped to chromosome 5, in a region devoid of mutations causing any comparable phenotype. We have isolated overlapping cDNAs from theHdh gene and compared their sequences with the human transcript. The consensus mouse coding sequence is 86% identical to the human at the DNA level and 91% identical at the protein level. Despite the overall high level of conservation,Hdh possesses an imperfect CAG repeat encoding only seven consecutive glutamines, compared to the 13–36 residues that are normal in man. Although no evidence for polymorphic variation of the CAG repeat was seen, a nearby CCG repeat differed in length by one unit between several strains of laboratory mouse andMus spretus. The absence of a long CAG repeat in the mouse is consistent with the lack of a spontaneous mouse model of HD. The information presented concerning the sequence of the mouse gene should facilitate attempts to create such a model.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Literature Cited
Martin, J.B., and Gusella, J.F. (1986).N. Engl. J. Med. 315:1267–1276.
Gusella, J.F., Wexler, N.S., Conneally, P.M., Naylor, S.L., Anderson, M.A., Tanzi, R.E., Watkins, P.C., Ottina, K., Wallace, M.R., Sakaguchi, A.Y., Young, A.B., Shoulson, I., Bonilla, E., and Martin, J.B. (1983).Nature 306:234–238.
Gusella, J.F., Tanzi, R.E., Anderson, M.A., Hobbs, W., Gibbons, K., Raschtchian, R., Gilliam, T.C., Wallace, M.R., Wexler, N.S., and Conneally, P.M. (1984).Science 225:1320–1326.
Gusella, J.F., and MacDonald, M.E. (1993). InMolecular Genetic Medicine, Vol. II, (ed.) Friedmann, T. (Academic Press, San Diego), pp. 139–158.
The Huntington's Disease Collaborative Research Group, Group 1: MacDonald, M.E., Ambrose, C.M., Duyao, M.P., Myers, R.H., Lin, C., Srinidhi, L., Barnes, G., Taylor, S.H., James, M., Groot, N., MacFarlane, H., Jenkins, B., Anderson, M.A., Wexler, N.S., and Gusella, J.F.; Group 2: Bates, G.P., Baxendale, S., Hummerich, H., Kirby, S., North, M., Youngman, S., Mott, R., Zehetner, G., Sedlacek, Z., Poustka, A., Frischauf, A.M., and Lehrach, H.; Group 3: Buckler, A.J., Church, D., Doucette-Stamm, L., O'Donovan, M.C., Riba-Ramirez, L., Shah, M., Stanton, V.P., Strobel, S.A., Draths, K.M., Wales, J.L., Dervan, P., and Housman, D.E.; Group 4: Altherr, M., Shiang, R., Thompson, L., Fielder, T., and Wasmuth, J.J.; Group 5: Tagle, D., Valdes, J., Elmer, L., Allard, M., Castilla, L., Swaroop, M., Blanchard, K., and Collins, F.S.; Group 6: Snell, R., Holloway, T., Gillespie, K., Datson, N., Shaw, D., and Harper, P.S. (1993).Cell 72:971–983.
Duyao, M., Ambrose, C., Myers, R., Novelletto, A., Persichetti, F., Frontali, M., Folstein, S., Ross, C., Franza, M., Abbott, M., Gray, J., Conneally, P., Young, A., Penney, J., Hollingsworth, Z., Shoulson, I., Lazzarini, A., Falek, A., Koroshetz, W., Sax, D., Bird, E., Vonsattel, J., Bonilla, E., Alvir, J., Bickham Conde, J., Cha, J.H., Dure, L., Gomez, S., Ramos, M., Sanchez-Ramos, J., Snodgrass, S., de Young, M., Wexler, N., Moscowitz, C., Penchaszadeh, G., MacFarlane, H., Anderson, M., Jenkins, B., Srinidhi, J., Barnes, G., Gusella, J.F., and MacDonald, M.E. (1993).Nature Genet. 4:387–392.
Snell, R.G., MacMillan, J.C., Cheadle, J.P., Fenton, I., Lazarou, L.P., Davies, P., MacDonald, M.E., Gusella, J.F., Harper, P.S., and Shaw, D.J. (1993).Nature Genet. 4:393–397.
Andrew, S.E., Goldberg, Y.P., Kremer, B., Telenius, H., Theilmann, J., Adam, S., Starr, E., Squitieri, F., Lin, B., Kalchman, M.A., Graham, R.K., and Hayden, M.R. (1993).Nature Genet. 4:398–403.
Rubinsztein, D.C., Leggo, J., Barton, D.E. and Ferguson-Smith, M.A. (1993).Nature Genet. 5:214–215.
MacDonald, M.E., Barnes, G., Srinidhi, J., Duyao, M.P., Ambrose, C.M., Myers, R.H., Gray, J., Conneally, P.M., Young, A., Penny, J., Shoulson, I., Hollingsworth, Z., Koroshetz, W., Bird, E., Vonsattel, J.P., Bonilla, E., Moscowitz, C., Penchaszadeh, G., Brzustowics, L., Alvir, J., Bickham-Conde, J., Cha, J.-H., Dure, L., Gomez, F., Ramos-Arroyo, M., Sanchez-Ramos, J., Snodgrass, S.R., de Young, M., Wexler, N.S., MacFarlane, H., Anderson, M.A., Jenkins, B., and Gusella, J.F. (1993).J. Med. Genet. 30:982–986.
Grosson, C.L.S., MacDonald, M.E., Duyao, M.P., Ambrose, C.M., Roffler-Tarlov, S., and Gusella, J.F. (1994).Mamm. Genome (in press).
Feinberg, A.P., and Vogelstein, B. (1984).Anal. Biochem. 137:266–267.
Sanger, T., Nicklen, S., and Coulson, A.R. (1977).Proc. Natl. Acad. Sci. U.S.A. 74:5463–5467.
Genetics Computer Group (1991). Program manual for the GCG package, version 7, April 1991, 575 Science Drive, Madison, Wisconsin 53711.
Ambrose, C.M., Duyao, M.P., Barnes, G., Bates, G.P., Lin, C.S., Srinidhi, J., Baxendale, S., Hummerich, H., Lehrach, H., Altherr, M., Wasmuth, J., Buckler, A., Church, D., Housman, D., Berks, M., Micklem, G., Durbin, R., Dodge, A., Read, A., Gusella, J., and MacDonald, M.E. (1994).Somat. Cell. Mol. Genet. 20:27–38.
Lin, B., Rommens, J.M., Graham, R.K., Kalchman, M., MacDonald, H., Nasir, J., Delaney, A., Goldberg, Y.P., and Hayden, M. (1993).Hum. Mol. Genet. 2:1541–1545.
Cheng, S.V., Martin, G.R., Nadeau, J.H., Haines, J.L., Bucan, M., Kozak, C.A., MacDonald, M.E., Lockyer, J.L., Ledley, F.D., Woo, S.L.C., Lehrach, H., Gilliam, T.C., and Gusella, J.F. (1989).Genomics 4:419–426.
Lin, B., Nasir, J., MacDonald, H., Hutchinson, G., Graham, R.K., Rommens, J.M., and Hayden, M. (1994).Hum. Mol. Genet. 3:85–92.
Wexler, N.S., Young, A.B., Tanzi, R.E., Travers, H., Starosta-Rubenstein, S., Penney, J.B., Snodgrass, S.R., Shoulson, I., Gomez, F., Ramos-Arroyo, M.A., Penchaszadeh, G., Moreno, R., Gibbons, K., Faryniarz, A. Hobbs, W., Anderson, M.A., Bonilla, E., Conneally, P.M., and Gusella, J.F. (1987).Nature,326:194–197.
Myers, R.H., Leavitt, J., Farrer, L.A., Jagadeesh, J., McFarlane, H., Mark, R.J., and Gusella, J.F. (1989).Am. J. Hum. Genet.,45:615–618.
Hoogeveen, A.T., Willemsen, R., Meyer, N., de Rooij, K.E., Roos, R.A.C., van Ommen, G., and Galjard, H. (1993).Hum. Mol. Genet. 2:2069–2073.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Barnes, G.T., Duyao, M.P., Ambrose, C.M. et al. Mouse Huntington's disease gene homolog (Hdh). Somat Cell Mol Genet 20, 87–97 (1994). https://doi.org/10.1007/BF02290678
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02290678