Mammalian Genome

, Volume 4, Issue 12, pp 711–715 | Cite as

Localization of Shaw-related K+ channel genes on mouse and human chromosomes

  • M. Haas
  • D. C. Ward
  • J. Lee
  • A. D. Roses
  • V. Clarke
  • P. D'Eustachio
  • D. Lau
  • E. Vega-Saenz de Miera
  • B. Rudy
Original Contributions


Four related genes, Shaker, Shab, Shaw, and Shal, encode voltage-gated K+ channels in Drosophila. Multigene subfamilies corresponding to each of these Drosophila genes have been identified in rodents and primates; this suggests that the four genes are older than the common ancestor of present-day insects and mammals and that the expansion of each into a family occurred before the divergence of rodents and primates.

In order to define these evolutionary relationships more precisely and to facilitate the search for mammalian candidate K+ channel gene mutations, we have mapped members of the Shaw-homologous gene family in humans and mice. Fluorescence in situ hybridization analysis of human metaphase chromosomes mapped KCNC2 (KShIIIA, KV3.2) and KCNC3 (KShIIID, KV3.3) to Chromosome (Chr) 19q13.3-q13.4. Inheritance patterns of DNA restriction fragment length variants in recombinant inbred strains of mice placed the homologous mouse genes on distal Chr 10 near Ms15-8 and Mdm-1. The mouse Kcnc1 (KShIIIB, NGK2-KV4, KV3.1) gene mapped to Chr 7 near Tam-1.

These results are consistent with the hypothesis that the generation of the mammalian KCNC gene family included both duplication events to generate family members in tandem arrays (KCNC2, KCNC3) and dispersion of family members to unlinked chromosomal sites (KCNC1). The KNCN2 and KCNC3 genes define a new synteny group between humans and mice.


Duplication Event Inbred Strain Metaphase Chromosome Channel Gene Mouse Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arnold, N., Bhatt, M., Ried, T., Ward, D.C., Wienberg, J. (1993). Fluorescence in-situ hybridization on banded chromosomes. In Techniques and Methods in Molecular Biology: Nonradioactive Labelling and Detection of Biomolecules, C. Kessler, ed. (New York, N.Y.: Springer-Verlag), in press.Google Scholar
  2. Blank, R.D., Campbell, G.R., Calabro, A., D'Eustachio, P. (1988). A linkage map of mouse Chromosome 12: localization of Igh and effects of sex and interference on recombination. Genetics 120, 1073–1083.Google Scholar
  3. Cahalan, M.D., Chandy, K.G., Grissner, S. (1991). Potassium channels in development, activation and disease in T lymphocytes. Current Topics in Membranes 39, 357–394.Google Scholar
  4. Chandy, K.G., Douglas, J., Gutman, G.A., Jan, L., Joho, R., Kaczmarek, L., McKinnon, D., North, R.A., Numa, S., Philipson, L., Ribera, A., Rudy, B., Salkoff, L., Swanson, R., Steiner, D., Tanouye, M., Tempel, B.L. (1991). A simplified gene nomenclature. Nature 352, 26.Google Scholar
  5. D'Eustachio, P., Jadidi, S., Fuhlbrigge, R.C., Gray, P.W., Chaplin, D.D. (1987). Interleukin-1 α and β genes: linkage on chromosome 2 in the mouse. Immunogenetics 26, 339–343.Google Scholar
  6. Ghanshani, S., Pak, M., McPherson, J.D., Strong, M., Dethlefs, B., Wasmuth, J.J., Salkoff, L., Gutman, G.A., Chandy, K.G. (1992). Genomic organization, nucleotide sequence, and cellular distribution of a Shaw-related potassium channel gene, Kv3.3, and mapping of Kv3.3 and Kv3.4 to human chromosomes 19 and 1. Genomics 12, 190–196.Google Scholar
  7. Green, M.C. (1989). A catalog of mutant genes and polymorphic loci. In Genetic Variants and Strains of the Laboratory Mouse, 2nd ed., M.F. Lyon, A.G. Searle, eds. (New York, N.Y.: Oxford University Press), pp. 12–403.Google Scholar
  8. Hille, B. (1992). Ionic Channels of Excitable Membranes, 2nd ed. (Sunderland, Mass.: Sinauer Associates).Google Scholar
  9. Jan, L.-Y., Y.-N. Jan (1990). How might the diversity of potassium channels be generated? Trends Neurosci 13, 415–419.Google Scholar
  10. Jeffreys, A.J., Wilson, V., Kelly, R., Taylor, B.A., Bulfield, G. (1987). Mouse DNA ‘fingerprints’: analysis of chromosome localization and germ-line stability of hypervariable loci in recombinant inbred strains. Nucleic Acids Res. 15, 2823–2836.Google Scholar
  11. Lichter, P., Chang Tang, C.J., Call, K., Hermanson, G., Evans, G.A., Housman, D., Ward, D.C. (1990). High resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones. Science 247, 64–69.Google Scholar
  12. Llinas, R. (1988). The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function. Science 242, 1654–1664.Google Scholar
  13. Luneau, C.J., Williams, J.B., Marshall, J., Levitan, E.S., Oliva, S., Smith, J.S., Antanavage, J., Folander, K., Stein, R.B., Swanson, R., Kaczmarek, L., Buhrow, S.A. (1991a). Alternative splicing contributes to K channel diversity in the mammalian central nervous system. Proc. Natl. Acad. Sci. USA 88, 3932–3936.Google Scholar
  14. Luneau, C.J., Wiedmann, R., Smith, J.S., Williams, J.B. (1991b). Shaw-like rat brain potassium channel cDNA's with divergent 3′ ends. FEBS Letters 288, 163–167.Google Scholar
  15. McCormack, T., Vega-Saenz de Miera, E., Rudy, B. (1990). Molecular cloning of a member of a third class of Shaker-family K+ channel genes in mammals. Proc. Natl. Acad. Sci. USA 87, 5227–5231.Google Scholar
  16. McKusick, V., Francomano, C., Antonarakis, S.E. (1990). Mendelian Inheritance in Man, 10th ed. (Baltimore, Md.: Johns Hopkins University Press).Google Scholar
  17. Nadeau, J.H. (1991). Genome duplication and comparative gene mapping. In Advanced Techniques in Chromosome Research, K.W. Adolph, ed. (New York, N.Y.: Marcel Dekker, Inc.), pp. 269–296.Google Scholar
  18. O'Brien, S.J., Womack, J.E., Lyons, L.A., Moore, K.J., Jenkins, N.A., Copeland, N.G. (1993). Anchored reference loci for comparative genome mapping in mammals. Nature Genet. 3, 103–112.Google Scholar
  19. Perney, T.M., Kaczmarek, L.K. (1991). The molecular biology of K+ channels. Curr. Opin. Cell Biol. 3, 663–670.Google Scholar
  20. Ried, T., Mahler, V., Vogt, P., Blonden, L., van Ommen, G.J.B., Cremer, T., Cremer, M. (1990). Direct carrier detection by in situ suppression hybridization with cosmid clones of the Duchenne/Becker muscular dystrophy locus. Hum. Genet. 85, 581–586.Google Scholar
  21. Ried, T., Lengauer, C., Cremer, T., Wiegant, J., Raap, A.K., Van der Ploeg, M., Groitl, P., Lipp, M. (1992a). Specific metaphase and interphase detection of the breakpoint region in 8q24 of Burkitt lymphoma cells by triple-color fluorescence in situ hybridization. Genes Chromosomes Cancer 4, 69–74.Google Scholar
  22. Ried, T., Baldini, A., Rand, T.C., Ward, D.C. (1992b). Simultaneous visualization of seven different DNA probes by in situ hybridization using combinatorial fluorescence and digital imaging microscopy. Proc. Natl. Acad. Sci. USA 89, 1388–1392.Google Scholar
  23. Ried, T., Rudy, B., Vega-Saenz de Miera, E., Lau, D., Ward, D.C., Sen, K. (1993). Localization of a highly conserved human potassium channel gene (NGK2-KV4; KCNC1) to chromosome 11p15. Genomics 15, 405–411.Google Scholar
  24. Rinchik, E.M., Magnuson, T., Holdener-Kenny, B., Kelsey, G., Bianchi, A., Conti, C.J., Chartier, F., Brown, K.A., Brown, S.D.M., Peters, J. (1992). Mouse Chromosome 7. Mammalian Genome 3 (Suppl) S104-S120.Google Scholar
  25. Rise, M.L., Frankel, W.N., Coffin, J.M., Seyfried, T.N. (1991). Genes for epilepsy mapped in the mouse. Science 253, 669–673.Google Scholar
  26. Rudy, B. (1988). Diversity and ubiquity of K+ channels. Neuroscience 25, 729–750.Google Scholar
  27. Rudy, B., Kentros, C., Vega-Saenz de Miera, E. (1991a). Families of K+ channel genes in mammals: toward an understanding of the molecular basis of K+ channel diversity. Mol. Cell. Neurosci 2, 89–102.Google Scholar
  28. Rudy, B., Sen, K., Vega-Saenz de Miera, E., Lau, D., Ried, T., Ward, D.C. (1991b). Cloning of a human cDNA expressing a high voltage-activating, TEA-sensitive, type-A K+ channel gene which maps to chromosome 1 band p21. J. Neurosci. Res. 29, 401–412.Google Scholar
  29. Rudy, B., Kentros, C., Weiser, M., Fruhling, D., Serodio, P., Vega Saenz de Miera, E., Ellisman, M.H., Pollock, J.A., Baker, H. (1992). Region-specific expression of a K+ channel gene in brain. Proc. Natl. Acad. Sci. USA 89, 4603–4607.Google Scholar
  30. Schroter, K.H., Ruppersberg, J.P., Wunder, F., Retig, J., Stockler, M., Pongs, O. (1991). Cloning and functional expression of a TEA-sensitive A-type potassium channel from rat brain. FEBS Lett. 278, 211–216.Google Scholar
  31. Silver, J. (1985). Confidence limits for estimates of gene linkage based on analysis of recombinant inbred strains. J. Hered. 76, 436–440.Google Scholar
  32. Skow, L. (1978). Genetic variation at a locus (Tam-1) for submaxillary gland protease in the mouse and its location on Chromosome 7. Genetics 90, 713–724.Google Scholar
  33. Taylor, B.A. (1978). Recombinant inbred strains. In Origins of Inbred Mice, H.C. Morse, III, ed. (New York, N.Y.: Academic Press), pp. 423–438.Google Scholar
  34. Taylor, B.A., Rowe, L., Grieco, D. (1992a). Close linkage of Mdm-1, a gene amplified and overexpressed in a transformed 3T3 cell line, with γ interferon (Ifg) on Chromosome 10 of the mouse. Mammalian Genome 3, 700–704.Google Scholar
  35. Taylor, B.A., Frankel, W.N., Reeves, R.H. (1992b). Mouse Chromosome 10. Mammalian Genome 3 (Suppl), S153-S161.Google Scholar
  36. Vega-Saenz de Miera, E., Moreno, H., Kentros, C., Rudy, B. (1992). Cloning of ShIII (Shaw-like) cDNAs encoding a novel high voltage-activating TEA-sensitive, type-A K+ channel. Proc. R. Soc. Lond. [Biol] 248, 9–18.Google Scholar
  37. Wei, A., Covarrubias, M., Butler, A., Baker K., Pak, M., Salkoff, L. (1990). K+ current diversity is produced by an extended gene family conserved in Drosophila and mouse. Science 248, 599–603.Google Scholar
  38. Yokoyama, S., Imoto, K., Kawamura, T., Higashida, H., Iwabe, N., Miyata, T., Numa, S. (1989). Potassium channels from NG108-15 neuroblastoma-glioma hybrid cells: primary structure and expression from cDNAs. FEBS Lett. 259, 37–43.Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1993

Authors and Affiliations

  • M. Haas
    • 1
  • D. C. Ward
    • 1
  • J. Lee
    • 2
  • A. D. Roses
    • 3
  • V. Clarke
    • 4
  • P. D'Eustachio
    • 4
  • D. Lau
    • 5
  • E. Vega-Saenz de Miera
    • 5
  • B. Rudy
    • 5
  1. 1.Department of GeneticsYale University School of MedicineNew HavenUSA
  2. 2.Department of PsychiatryDuke University Medical CenterDurhamUSA
  3. 3.Division of NeurologyDuke University Medical CenterDurhamUSA
  4. 4.Department of BiochemistryNew York University Medical CenterNew YorkUSA
  5. 5.Department of Physiology and BiophysicsNew York University Medical CenterNew YorkUSA

Personalised recommendations