Abstract
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.
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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.
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.
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.
Beechey, C.V., Searle, A.G. (1986). Crossing over between the Rw and W loci. Mouse News Lett. 75, 27.
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.
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.
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.
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.
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.
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.
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.
Feinberg, A.P., Vogelstein, B. (1983). A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal. Biochem. 132, 6–13.
Flanagan, J.G., Leder, P. (1990). The kit ligand: a cell surface molecule altered in steel mutant fibroblasts. Cell 63, 185–194.
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.
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.
Grüneberg, H. (1952). The Genetics of the Mouse, 2nd ed. (The Hague: Nijhoff).
Grüneberg, H., Truslove, G.M. (1960). Two closely linked genes in the mouse. Genet. Res. 1, 69–90.
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.
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.
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.
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.
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.
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.
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.
Kozak, C.A., Stephenson, D.A. (1993). Chromosome 5 committee report. Mammalian Genome 4 (Suppl.), S72-S87.
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.
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.
Lusis, A.J., Paigen, K. (1978). The large scale isolation of mouse β-glucuronidase and comparison of allozymes. J. Biol. Chem. 253, 7336–7345.
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.
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.
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.
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.
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.
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.
Petras, M.L. (1972). An inherited albumin variant in the mouse, Mus musculus. Biochem. Genet. 7, 273–277.
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.
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.
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.
Searle, A.G., Phillips, R.J.S. (1967). Genetic effects of high-LET radiation in mice. Radiat. Res. 7, 294–303.
Searle, A.G., Truslove, G.M. (1970). A gene triplet in the mouse. Genet. Res. 15, 227–235.
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.
Spencer, N., Hopkinson, D.A., Harris, H. (1964). Phosphoglucomutase polymorphism in man. Nature 204, 742–745.
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.
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.
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.
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.
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Stephenson, D.A., Lee, KH., Nagle, D.L. et al. Mouse rump-white mutation associated with an inversion of Chromosome 5. Mammalian Genome 5, 342–348 (1994). https://doi.org/10.1007/BF00356552
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DOI: https://doi.org/10.1007/BF00356552