Mammalian Genome

, Volume 5, Issue 6, pp 342–348 | Cite as

Mouse rump-white mutation associated with an inversion of Chromosome 5

  • D. A. Stephenson
  • K.-H. Lee
  • D. L. Nagle
  • C.-H. Yen
  • A. Morrow
  • D. Miller
  • V. M. Chapman
  • M. Bućan
Original Contributions


The rump-white (Rw) mutation in the mouse was previously mapped as part of a cluster of spotting genes on Chromosome (Chr) 5 that includes the dominant spotting (W) and patch (Ph) loci. Recent studies have shown that the W locus encodes the KIT tyrosine kinase cell surface receptor and that Ph is a deletional mutation encompassing the platelet-derived growth factor receptor alpha subunit (Pdgfra) gene. However, the molecular basis of the Rw mutation remains to be established. We have analyzed an interspecific Mus spretus backcross segregating Rw and several loci proximal and distal to the W/Ph/Rw region to study the basis of this mutation. These studies indicated that loci within the En2 to Kit region of the chromosome do not recombine with one another even though they have been separated in other mapping studies presented here and elsewhere. We conducted a series of fluorescent in situ hybridization (FISH) studies with genomic probes to En2, Msx1, D5Buc1, and Kit to compare the physical order of these loci on the Rw and wild-type chromosomes. The Kit locus mapped to approximately the same region on both chromosomes of the Rw heterozygotes, while the positions of En2, Msx1, and D5Buc1 were reversed on the two chromosomes. Taken together, both the genetic and physical mapping data establish that the Rw mutation is associated with an inversion involving loci in the proximal region of Chromosome 5.


Proximal Region Alpha Subunit Physical Order Genomic Probe Factor Receptor Alpha 
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. Anderson, D.M., Lyman, S.D., Baird, A., Wignall, J.M., Eisenman, J., Rauch, C., March, C.J., Boswell, H.S., Gimpel, S.D., Cosman, D., Williams, D.E. (1990). Molecular cloning of mast cell growth factor, a hematopoietin that is active in both membrane bound and soluble forms. Cell 63, 235–243.Google Scholar
  2. Artzt, K., Shin, H.S., Bennett, D. (1982). Gene mapping within the T/t complex of the mouse. II anomalous position of the H-2 complex in t haplotypes. Cell 28, 471–476.Google Scholar
  3. Batchelor, A.L., Phillips, R.J.S., Searle, A.G. (1966). A comparison of the mutagenic effectiveness of chronic neutron- and γ-irradiation of mouse spermatogonia. Mutat. Res. 3, 218–229.Google Scholar
  4. Beechey, C.V., Searle, A.G. (1986). Crossing over between the Rw and W loci. Mouse News Lett. 75, 27.Google Scholar
  5. Cattanach, B.M., Burtenshaw, M.D., Rasberry, C., Evans, E.P. (1993). Large deletions and other gross forms of chromosome imbalance compatible with viability and fertility in the mouse. Nature Genet. 3, 56–61.Google Scholar
  6. Chabot, B., Stephenson, D.A., Chapman, V.M., Besmer, P., Bernstein, A. (1988). The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature 335, 88–89.Google Scholar
  7. Chin, H., Mock, B., Kim, H.-L., Kim, H., Kozak, C.A. (1992). The gene for the dihydropyridine-sensitive calcium channel α2 subunit (CCHL2A) maps to the proximal region of mouse Chromosome 5. Genomics 13, 1325–1327.Google Scholar
  8. Copeland, N.G., Gilbert, D.J., Cho, B.C., Donovan, P.J., Jenkins, N.A., Cosman, D., Anderson, D., Lyman, S.D., Williams, D.E. (1990). Mast cell growth factor maps to the steel locus on mouse chromosome 10 and is deleted in a number of steel alleles. Cell 63, 175–183.Google Scholar
  9. Davisson, M.T., Lewis, S.E. (1990). Chromosome aberrations associated with induced mutations: effect on mapping new mutations. In Banbury Report 34: Biology of Mammalian Germ Cell Mutagenesis J.W. Allen, B.A. Briggs. M.F. Lyon, M.J. Moses, L.B. Russell, eds. (Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press). pp. 195–205.Google Scholar
  10. Dietrich, W., Katz, H., Lincoln, S.E., Shin, H.-S., Friedman, J., Dracopoli, N.C., Lander, E.C. (1992). A genetic map of the mouse suitable for typing intraspecific crosses. Genetics 131, 423–447.Google Scholar
  11. Duttlinger, R., Manova, K., Chu, T.Y., Gyssler, C., Zelenetz, A.D., Bachvarova, R.F., Besmer, P. (1983) W-sash affects positive and negative elements controlling c-kit expression: ectopic c-kit expression at sites of kit-ligand expression affects melanogenesis. Development 118, 705–717.Google Scholar
  12. Feinberg, A.P., Vogelstein, B. (1983). A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal. Biochem. 132, 6–13.Google Scholar
  13. Flanagan, J.G., Leder, P. (1990). The kit ligand: a cell surface molecule altered in steel mutant fibroblasts. Cell 63, 185–194.Google Scholar
  14. Geissler, E.N., Ryan, M.A., Housman, D.E. (1988a). The dominant white spotting (W) locus of the mouse encodes the c-kit proto-oncogene. Cell 55, 185–192.Google Scholar
  15. Geissler, E.N., Cheng, S.V., Gusella, J.F., Housman, D.E. (1988b). Genetic analysis of the dominant white-spotting (W) region on mouse chromosome 5: identification of cloned DNA markers near W. Proc. Natl. Acad. Sci. USA 85, 9635–9639.Google Scholar
  16. Grüneberg, H. (1952). The Genetics of the Mouse, 2nd ed. (The Hague: Nijhoff).Google Scholar
  17. Grüneberg, H., Truslove, G.M. (1960). Two closely linked genes in the mouse. Genet. Res. 1, 69–90.Google Scholar
  18. Gupta, P., Rosen, J.M., D'Eustachio, P., Ruddle, F.H. (1982). Localization of the casein gene family to a single mouse chromosome. J. Cell Biol. 93, 199–204.Google Scholar
  19. Hammer, M.F., Schimenti, J., Silver, L.M. (1989). Evolution of mouse chromosome 17 and the origin of inversions associated with t haplotypes. Proc Natl. Acad. Sci. USA 86, 3261–3265.Google Scholar
  20. Hammer, R.E., Krumlauf, R., Camper, S.A., Brinster, R.L., Tilghman, S.M. (1987). Diversity of alpha-fetoprotein gene-expression in mice is generated by a combination of separate enhancer elements. Science 235, 53–58.Google Scholar
  21. Herrmann, B.G., Bucan, M., Mains, P.E., Frischauf, A.-M., Silver, L.M., Lehrach, H. (1986). Genetic analysis of the proximal portion of the mouse t complex: evidence for a second inversion within t haplotypes. Cell 44, 469–476.Google Scholar
  22. Herrmann, B.G., Barlow, D.P., Lehrach, H. (1987). A large inverted duplication allows homologous recombination between chromosomes heterozygous for the proximal t complex inversion. Cell 48, 813–825.Google Scholar
  23. Huang, E., Nocka, K., Beier, D.R., Chu, T.Y., Buck, J., Lahm, H.W., Wellner, D., Leder, P., Besmer, P. (1990). The hematopoietic growth factor KL is encoded by the SL locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell 63, 225–233.Google Scholar
  24. Joyner, A.L., Martin, G.R. (1987). En-1 and En-2, two mouse genes with sequence homology to the Drosophila engrailed genes; expression during embryogenesis. Genes Dev. 1, 29–38.Google Scholar
  25. Kozak, C.A., Stephenson, D.A. (1993). Chromosome 5 committee report. Mammalian Genome 4 (Suppl.), S72-S87.Google Scholar
  26. Lichter, P., Cremer, T., Bordon, J., Manuelidis, L., Ward, D.C. (1988). Deletion of individual human chromosomes in metaphase and interphase cells by in situ suppression hybridization using recombinant DNA libraries. Hum. Genet. 80, 224–234.Google Scholar
  27. Lichter, P., Tang, C.J.C., 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
  28. Lusis, A.J., Paigen, K. (1978). The large scale isolation of mouse β-glucuronidase and comparison of allozymes. J. Biol. Chem. 253, 7336–7345.Google Scholar
  29. Lyon, M.F., Glenister, P.H., Loutit, J.F., Evans, E.P., Peters, J. (1984). A presumed deletion covering the W and Ph loci of the mouse. Genet. Res. 44, 161–168.Google Scholar
  30. Mercola, M., Wang, C., Kelly, J., Browntee, C., Jackson-Grusby, L., Stiles, C., Bowen-Pope, D.F. (1990). Selective expression of PDGF A and its receptor during early mouse embryogenesis. Dev. Biol. 138, 114–122.Google Scholar
  31. Mock, B.A., Nordan, R.P., Justice, M.J., Kozak, C., Jenkins, N.A., Copeland, N.G., Clark, S.C., Wong, G.G., Rudikoff, S. (1989). The murine Il-6 gene maps to the proximal region of chromosome 5. J. Immunol. 142, 1372–1376.Google Scholar
  32. Mullins, L.J., Grant, S.G., Stephenson, D.A., Chapman, V.M. (1988). Multilocus molecular mapping of the mouse X chromosome. Genomics 3, 187–194.Google Scholar
  33. Mullins, L.J., Stephenson, D.A., Grant, S.G., Chapman, V.M. (1990). Efficient linkage of 10 loci in the proximal region of the mouse X chromosome. Genomics 7, 19–30.Google Scholar
  34. Nocka, K., Majumder, S., Chabot, B., Ray, P., Cervone, M., Bernstein A., Besmer, P. (1990). Expression of c-kit gene products in known cellular targets of W mutations in normal and W mutant mice-evidence for an impaired c-kit kinase in mutant mice. Genes Dev. 3, 816–826.Google Scholar
  35. Petras, M.L. (1972). An inherited albumin variant in the mouse, Mus musculus. Biochem. Genet. 7, 273–277.Google Scholar
  36. Qui, F., Ray, P., Brown, K., Barker, P.E., Jhanwar, S., Ruddle, F.H., Besmer, P. (1988). Primary structure of c-kit: relationship with the CSF-1/PDGF receptor kinase family—oncogenic activation of v-kit involves deletion of extracellular domain and C terminus. EMBO J. 7, 1003–1011.Google Scholar
  37. Reith, A.D., Rottapel, R., Giddens, E., Brady, C., Forrester, L., Bernstein, A. (1990). W mutant mice with mild or severe developmental defects contain distinct point mutations in the kinase domain of the c-kit transmembrane receptor. Genes Dev. 4, 390–400.Google Scholar
  38. Searle, A.G. (1989). Chromosomal variants: numerical variants and structural rearrangements. In Genetic Variants and Strains of the Laboratory Mouse, M.F. Lyon, A.G. Searle, eds. (New York: Oxford University Press), pp. 589–616.Google Scholar
  39. Searle, A.G., Phillips, R.J.S. (1967). Genetic effects of high-LET radiation in mice. Radiat. Res. 7, 294–303.Google Scholar
  40. Searle, A.G., Truslove, G.M. (1970). A gene triplet in the mouse. Genet. Res. 15, 227–235.Google Scholar
  41. Smith, E.A., Seldin, M.F., Martinez, L., Watson, M.L., Choudhury, G.G.. Lalley, P.A., Pierce, J., Aaronson, S., Barker, J., Naylor, S.L., Sakaguchi, A.Y. (1991). Mouse platelet-derived growth factor receptor gene is deleted in W 19H and patch mutations on chromosome 5. Proc. Natl. Acad. Sci. USA 88, 4811–4815.Google Scholar
  42. Spencer, N., Hopkinson, D.A., Harris, H. (1964). Phosphoglucomutase polymorphism in man. Nature 204, 742–745.Google Scholar
  43. Stephenson, D.A., Mercola, M., Anderson, C., Wang, C., Stiles, C.D., Bowen-Pope, D.F., Chapman, V.M. (1991). Platelet-derived growth factor receptor α-sununit gene (Pdgfra) is deleted in the mouse patch (Ph) mutation. Proc. Natl. Acad. Sci. USA 88, 6–10.Google Scholar
  44. Swank, R.T., Moore, K., Chapman, V.M. (1987). Abnormal subcellular distribution of β-glucuronidase in mice with a genetic alteration in enzyme structure. Biochem. Genet. 25, 161–174.Google Scholar
  45. Tan, J.C., Nocka, K., Ray, P., Traktman, P., Besmer, P. (1990). The dominant W 42 spotting phenotype results from a missense mutation in the c-kit receptor kinase. Science 247, 209–212.Google Scholar
  46. Zsebo, K.M., Wypych, J., McNiece, I.K., Lu, H.S., Smith, K.A., Karkare, S.B., Sachdev, R.K., Yuschenkoff, V.N., Birkett, N.C., Williams, L.R., Satyagal, V.N., Tung, W., Bosselman, R.A., Mendiaz, E.A., Langley, K.E. (1990). Identification, purification, and biological characterization of hematopoietic stem cell factor from buffalo rat liver-conditioned medium. Cell 63, 195–201.Google Scholar

Copyright information

© Springer-Verlag New York Inc 1994

Authors and Affiliations

  • D. A. Stephenson
    • 1
  • K.-H. Lee
    • 1
  • D. L. Nagle
    • 2
  • C.-H. Yen
    • 1
  • A. Morrow
    • 1
  • D. Miller
    • 1
  • V. M. Chapman
    • 1
  • M. Bućan
    • 2
  1. 1.Department of Molecular and Cellular BiologyRoswell Park Cancer InstituteBuffaloUSA
  2. 2.Department of PsychiatryUniversity of PennsylvaniaPhiladelphiaUSA

Personalised recommendations