Abstract
Epidemiological data and genetic studies indicate that certain forms of human epilepsy are inherited. Based on the similarity between the human and mouse genomes, mouse models of epilepsy could facilitate the discovery of genes associated with epilepsy syndromes. Here, we report an insertional murine mutation that inactivates a novel gene and results in whole body jerks, generalized clonic seizures, and epileptic brain activity in transgenic mice. The gene, named jerky, encodes a putative 1.7 kD protein displaying homology to a number of nuclear regulatory proteins, suggesting that perhaps the jerky protein is able to bind DNA.
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References
Delgado-Escueta, A.V., Ward, A.A., Woodbury, D.M. & Porter, R.G. New wave of research in the epilepsies. in Advances in Neurology, Basic mechanisms of the epilepsies. Molecular and cellular approaches. (eds Delgado-Escueta, A.V., Ward, A.A., Woodbury, D.M. & Porter, R.G.) 44, 3–55 (Raven Press, New York, 1986).
Shoffner, J.M. et al. Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation. Cell 61, 931–937 (1990).
Beck, C. et al. A nonsense mutation in the α4 subunit of the nicotinergic acetylcholine receptor (CHRNA4) cosegregates with 20q-linked benign neonatal familial convulsions (EBN1). Neurobiol. Dis. 1, 95–99 (1994).
Philips, H.A., Scherfer, I.E., Berkovic, S.F., Hollway, G.E., Sutherland, G.R. & Mulley, J.C. Localization of a gene for autosomal dominant nocturnal frontal lobe epilepsy to chromosome 20q 13.2. Nature Genet. 10, 117–118 (1995).
Lehesjoki, A.E. et al. Linkage studies in progressive myoclonus epilepsy: Unverricht-Lundborg and Lafora's diseases. Neurology 42, 1545–1550 (1992).
Greenberg, D.A. & Delgado-Escueta, A.V. The chromosome 6p epilepsy locus: exploring mode of inheritance and heterogeneity through linkage analysis. Epilepsia 34, S12–S18 (1993).
Weissbecker, K.A. et al. Confirmation of linkage between juvenile myoclonic epilepsy locus and the HLA region of chromosome 6. Am. J. med. Genet. 38, 32–36 (1991).
Ottman, R. et al. Localization of a gene for partial epilepsy to chromosome 10q. Nature Genet. 10, 56–60 (1995).
Garey, C.E., Schwarzman, A.L., Rise, M.L. & Seyfried, T.N. Ceruloplasmin gene defect associated with epilepsy in EL mice. Nature Genet. 6, 426–431 (1994).
Tecott, L.H. et al. Eating disorder and epilepsy in mice lacking 5-HT2C serotonin receptors. Nature 374, 542–546 (1995).
Toth, M., Shenk, T. & Madarasz, E. Differentiation is induced in three dimensional cultures of brain cells immortalized by the lap mammalian regulatory system. J. neurosci. Res. 41, (in the press).
Racine, R.J. Modification of seizure activity by electrical stimulation. II. Motor seizure. Clin. Neurophysiol. 32, 281–294 (1972).
Rowe, L.B. et al. Maps from two interspecific backcross DNA panels available as a community genetic mapping resource. Mamm. Genome 5, 253–274 (1994).
Lossie, A.C., Gordon, D.F. & Camper, S.A. Localization of thyrotropin-releasing hormone receptor and thyrotroph embryonic factor on mouse chromosome 15. Mamm. Genome 4, 621–623 (1993).
Altschul, S.F., Gish, W., Miller, W., Myers, E.W. & Lipman, D.J. Basic local alignment search tool. J. molec. Biol. 215, 403–410 (1990).
Earnshaw, W.C. et al. Molecular cloning of cDNA for CENP-B, the major human centromere autoantigen. J. Cell Biol. 104, 817–829 (1987).
Yoda, K., Kitagawa, K., Masumoto, H., Muro, Y. & Okazaki, T. A human centromere protein, CENP-B, has a DNA binding domain containing four potential alpha helices at the NH2 terminus, which is separable from dimerizing activity. J. Cell Biol. 119, 1413–1427 (1992).
Tudor, M., Lobocka, M., Goodell, M., Pettitt, J. & O'Hare, K. The pogo transposable element family of Drosophila melanogaster. Molec. Gen. Genet. 232, 126–134 (1992).
Hohmann, S. Characterisation of PDC2, a gene necessary for high level expression of pyruvate decarboxylase structural genes in Saccharomyces cerevisiae. Molec. Gen. Genet. 241, 657–666 (1993).
Noebels, J.L. A single gene error of noradrenergic axon growth synchronizes central neurones. Nature 310, 409–411 (1984).
Noebels, J.L., Qiao, X., Bronson, R.T., Spencer, C. & Davisson, M.T. Stargazer: a new neurological mutant on chromosome 15 in the mouse with prolonged cortical seizures. Epilepsy Res. 7, 129–135 (1990).
McNamara, J.O. Cellular and molecular basis of epilepsy. J. Neurosci. 14, 3413–3425 (1994).
Labow, M.A., Baim, S.B., Shenk, T. & Levine, A.J. Conversion of the lac repressor into an allosterically regulated transcriptional activator for mammalian cells. Molec. cell. Biol. 10, 3343–3356 (1990).
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Toth, M., Grimsby, J., Buzsaki, G. et al. Epileptic seizures caused by inactivation of a novel gene, jerky, related to centromere binding protein–B in transgenic mice. Nat Genet 11, 71–75 (1995). https://doi.org/10.1038/ng0995-71
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DOI: https://doi.org/10.1038/ng0995-71
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