Behavior Genetics

, Volume 20, Issue 2, pp 307–323

Mapping of two genes that influence susceptibility to audiogenic seizures in crosses of C57BL/6J and DBA/2J mice

  • Paul E. Neumann
  • Thomas N. Seyfried
Regular Articles


The difference in susceptibility to audiogenic seizures (AGS) between C57BL/6J and DBA/2J inbred strains of mice is due to multiple genetic factors. AGS susceptibility was tested in 21-day-old mice from classical crosses, BXD recombinant inbred (RI) strains, a congenic DBA/2N.B6N-Ahb inbred strain and crosses between the BXD RI strains and DBA/2J. Analysis of these data reveals that the variation in AGS susceptibility between these two strains results from allelic differences at three or more loci. Most of the variation is due to allelic differences at two loci. The first,Asp-1 (formerlyIas), is a major gene located on chromosome 12, betweenAh andD12 Nyul. The second,Asp-2 (formerlyasp), is a minor gene located on chromosome 4, tightly linked tob. The negative correlation of brain stem Ca2+-ATPase activity and AGS susceptibility in the BXD RI strains suggests that the strain difference in Ca2+-ATPase activity is inherited as a polygenic trait and thatAsp-1 andAsp-2 are linked to, or identical to, factors that influence Ca2+-ATPase activity.

Key Words

audiogenic seizures C57BL/6J inbred mice DBA/2J inbred mice recombinant inbred strains epilepsy Ca2+-ATPase 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ault, B., and Wang, C. M. (1986). Adenosine inhibits epileptiform activity arising in hippocampal area CA3.Br. J. Pharmacol. 87:695–703.Google Scholar
  2. Bailey, D. W. (1978). Sources of subline divergence and their relative importance for sublines of six major inbred strains of mice. In Morse, H. C., III (ed.),Origins of Inbred Mice, Academic Press, New York, pp. 197–215.Google Scholar
  3. Carey, G. (1988). Inference about genetic correlations.Behav. Genet. 18:329–338.Google Scholar
  4. Cobb, R. R., Stoming, T. A., and Whitney, J. B., III (1987). The aryl hydrocarbon hydroxylase (Ah) locus and a novel restriction-fragment length polymorphism (RFLP) are located on mouse chromosome 12.Biochem. Genet. 25:401–413.Google Scholar
  5. Coleman, D. L. (1960). Phenylalanine hydroxylase activity in dilute and nondilute strains of mice.Arch. Biochem. Biophys. 91:300–306.Google Scholar
  6. Collins, R. L. (1970). A new genetic locus mapped from behavioral variation in mice: Audiogenic seizure prone (asp).Behav. Genet. 1:99–109.Google Scholar
  7. Collins, R. L. (1972). Audiogenic seizures. In Purpura, D. P., Penry, J. K., Tower, D. B., Woodbury, D. M., and Walter, R. D. (eds),Experimental Models of Epilepsy: A Manual for the Laboratory Worker, Raven Press, New York, pp. 347–372.Google Scholar
  8. Collins, R. L. (1974). Maltese dilution, chromosome 9, and audiogenic seizures in DBA/2 mice: experimental evaluation.Brain Res. 70:541–546.Google Scholar
  9. Collins, R. L., and Fuller, J. L. (1968). Audiogenic seizure prone (asp): A gene affecting behavior in linkage group VIII of the mouse.Science 162:1137–1139.Google Scholar
  10. Davisson, M. T., and Roderick, T. H. (1981). Recombination percentages. In Green, M. C. (ed.),Genetic Variants and Strains of the Laboratory Mouse, Gustav Fischer Verlag, Stuttgart, pp. 283–313.Google Scholar
  11. Davisson, M. T., Roderick, T. H., Hillyard, A. L., and Doolittle, D. P. (1988). Linkage map of the mouse.Mouse News Lett. 81:12–19.Google Scholar
  12. D'Eustachio, P. (1984). A genetic map of mouse chromosome 12 composed of polymorphic DNA fragments.J. Exp. Med. 160:827–838.Google Scholar
  13. Dunwiddie, T. V., and Worth, T. (1982). Sedative and anticonvulsant effects of adenosine analogs in mouse and rat.J. Pharmacol. Exp. Ther. 220:70–76.Google Scholar
  14. Ferrendelli, J. A. (1984). Roles of biogenic amines and cyclic nucleotides in seizure mechanisms.Ann. Neurol. 16 (Suppl.):S98-S103.Google Scholar
  15. Fuller, J. L., and Sjursen, F. H., Jr. (1967). Audiogenic seizures in eleven mouse strains.J. Hered. 58:135–140.Google Scholar
  16. Fuller, J. L., Easler, C., and Smith, M. E. (1950). Inheritance of audiogenic seizure susceptibility in the mouse.Genetics 35:622–632.Google Scholar
  17. Ginsburg, B. E., and Miller, D. S. (1963). Genetic factors in audiogenic seizures. In Busnel, R. G. (ed.),Colloques Internationaux du Centre National de la Recherche Scientifique No. 112: Psychopathologie, Neuropharmacologie et Biochimie de la Crise Audiogene, Editions du Centre National de la Recherche Scientifique, Paris, pp. 217–225.Google Scholar
  18. Ginsberg, B. E., Cowen, J. S., Maxson, S. C., and Sze, P. Y. (1967). Biochemical effects of gene mutations associated with audiogenic seizures.Excerpta Med. Int. Congr. Ser. 175:695–701.Google Scholar
  19. Hall, C. S. (1947). Genetic differences in fatal audiogenic seizures between two inbred strains of house mice.J. Hered. 38:2–6.Google Scholar
  20. Henry, K. R. (1986). Audiogenic seizures in relation to genetically and experimentally produced cochlear pathology. In Fuller, J. L., and Simmel, E. C. (ed.),Perspectives in Behavior Genetics, Lawrence Erlbaum Associates, Hillsdale, NJ, pp. 57–93.Google Scholar
  21. Huff, S. D., and Huff, R. L. (1962). Dilute locus and audiogenic seizures in mice.Science 136: 318–319.Google Scholar
  22. Huff, S. D., and Fuller, J. L. (1964). Audiogenic seizures, the dilute locus, and phenylalanine hydroxylase in DBA/1 mice.Science 144:304–305.Google Scholar
  23. Hume, R. I., and Honig, M. G. (1986). Excitatory action of ATP on embryonic chick muscle.J. Neurosci. 6:681–690.Google Scholar
  24. International Committee on Standardized Genetic Nomenclature for Mice (1985). Rules for nomenclature of genes, chromosome anomalies and inbred strains.Mouse News Lett. 72:2–28.Google Scholar
  25. Jahr, C. E., and Jessell, T. M. (1983). ATP excites a subpopulation of rat dorsal horn neurones.Nature 304:730–733.Google Scholar
  26. Laird, H. E., II, Dailey, J. W., and Jobe, P. C. (1984). Neurotransmitter abnormalities in genetically epileptic rodents.Fed. Proc. 43:2505–2509.Google Scholar
  27. Legraverend, C., Karenlampi, S. O., Bigelow, S. W., Lalley, P. A., Kozak, C. A., Womack, J. E., and Nebert, D. W. (1984). Aryl hydrocarbon hydroxylase induction by benzo[a]anthracene: Regulatory gene localized to the distal portion of mouse chromosome 17.Genetics 107:447–461.Google Scholar
  28. Maitre, M., Ciesielski, L., Lehmann, A., Kempf, E., and Mandel, P. (1974). Protective effect of adenosine and nicotinamide against audiogenic seizure.Biochem. Pharmacol. 23:2807–2816.Google Scholar
  29. Nebert, D. W., (1980). Pharmacogenetics: An approach to understanding chemical and biological aspects of cancer.J. Natl. Cancer Inst. 64:1279–1290.Google Scholar
  30. Neumann, P. E., Seyfried, T. N., and Collins, R. L. (1989). Nomenclature changes for audiogenic seizure susceptibility genes.Mouse News Lett. 83:157.Google Scholar
  31. Palayoor, S. T., and Seyfried, T. N. (1984). Genetic association between Ca2+-ATPase activity and audiogenic seizures in mice.J. Neurochem. 42:1771–1774.Google Scholar
  32. Palayoor, S. T., Seyfried, T. N., and Bernard, D. J. (1986). Calcium ATPase activities in synaptic plasma membranes of seizure-prone mice.J. Neurochem. 46:1370–1375.Google Scholar
  33. Roderick, T., and Davisson, M. T. (1987). Nomenclature change: Ias to asp-1.Mouse News Lett. 77:106.Google Scholar
  34. Schlesinger, K., Elston, R. C., and Boggan, W. (1966). The genetics of sound induced seizure in inbred mice.Genetics 54:95–103.Google Scholar
  35. Seyfried, T. N. (1979). Audiogenic seizures in mice.Fed. Proc. 38:2399–2404.Google Scholar
  36. Seyfried, T. N. (1982a). Convulsive disorders. In Foster, H. L., Small, J. D., and Fox, J. C. (eds.),The Mouse in Biomedical Research, Vol. 4, Academic Press, Orlando, FL, pp. 97–124.Google Scholar
  37. Seyfried, T. N. (1982b). Developmental genetics of audiogenic seizure susceptibility in mice. In Anderson, V. E., Hauser, W. A., Penry, J. K., and Sing, C. F. (eds.),Genetic Basis of the Epilepsies, Raven Press, New York, pp. 199–210.Google Scholar
  38. Seyfried, T. N. (1983). Genetic heterogeneity for the development of audiogenic seizures in mice.Brain Res. 271:325–329.Google Scholar
  39. Seyfried, T. N., and Glaser, G. H. (1981). Genetic linkage between the Ah locus and a major gene that inhibits susceptibility to audiogenic seizures in mice.Genetics 99:117–126.Google Scholar
  40. Seyfried, T. N., Glaser, G. H., and Yu, R. K. (1978). Cerebral, cerebellar and brainstem gangliosides in mice susceptible to audiogenic seizures.J. Neurochem. 31:21–27.Google Scholar
  41. Seyfried, T. N., Yu, R. K., and Glaser, G. H. (1980). Genetic analysis of audiogneic seizures susceptibility in C57BL/6J×DBA/2J recombinant inbred strains of mice.Genetics 94:701–718.Google Scholar
  42. Seyfried, T. N., Glaser, G. H., Yu, R. K., and Palayoor, S. T. (1986). Inherited convulsive disorders in mice. In Delgado-Escueta, A. V., Ward, A. A., Jr., Woodbury, D. M., and Porter, J. R. (eds.),Advances in Neurology, Vol. 44, Raven Press, New York, pp. 115–133.Google Scholar
  43. Silver, J. (1985). Confidence limits for estimates of gene linkage based on analysis of recombinant inbred strains.J. Hered. 76:436–440.Google Scholar
  44. Taylor, B. A. (1988). BXD-32 RI strain contaminated.Mouse News Lett. 81:72.Google Scholar
  45. Wieraszko, A., and Seyfried, T. N. (1989). Increased amount of extracellular ATP in stimulated hippocampal slices of seizure prone mice.Neurosci. Lett. 106:287–293.Google Scholar
  46. Wieraszko, A., Goldsmith, G., and Seyfried, T. N. (1989). Stimulation dependent release of ATP from hippocampal slices.Brain Res. 485:244–250.Google Scholar
  47. Witt, G., and Hall, C. S. (1949). The genetics of audiogenic seizures in the house mouse.J. Comp. Physiol. Psychol. 42:58–63.Google Scholar
  48. Wood, A. W., and Taylor, B. A. (1979). Genetic regulation of coumarin hydroxylase activity in mice: Evidence for single locus control on chromosome 7.J. Biol. Chem. 254:5647–5661.Google Scholar

Copyright information

© Plenum Publishing Corporation 1990

Authors and Affiliations

  • Paul E. Neumann
    • 1
    • 2
  • Thomas N. Seyfried
    • 3
  1. 1.Department of NeurologyChildren's HospitalBoston
  2. 2.Department of NeuropathologyHarvard Medical SchoolUSA
  3. 3.Department of BiologyBoston CollegeChestnut Hill
  4. 4.Neurology Research LaboratoriesChildren's HospitalBoston

Personalised recommendations