Abstract
Mutations at the recessive reeler locus (rl) on mouse Chromosome (Chr) 5 result in abnormal development of multiple central nervous system components, including the cerebral and cerebellar cortices. These abnormalities are characterized by highly disorganized laminar structures thought to have arisen from a post-migration failure of neuronal organization events that are probably mediated through cell-cell interactions. As a result of a mutagenesis scheme designed to generate visible recessive mutations induced by the drug chlorambucil, we had previously recovered a new allele of the reeler locus (rl Alb) that is likely to involve a deletion based on the known mechanisms of chlorambucil action. We have constructed a high-resolution genetic map from two intercrosses segregating this allele. Our first cross, in which the mutation was outcrossed to the 101 strain prior to intercrossing, consisted of 196 meioses and resulted in the positioning of four loci proximal to rl, with D5Mit1 being the closest (2.6±1.1 cM). The second cross consisted of intercrossing rl heterozygotes derived from an outcross to the C57BL/6 strain. A total of 318 mice (636 meioses) gave rise to a panel of 41 recombinants, which were used to map a total of 14 loci within a 6.4-cM interval bounded by D5Mit1 and the En-2 gene. A yeast artificial chromosome contig consisting of clones containing two of these loci, D5Mit72 (located 0.31 cM distal to rl), and D5Mit61 (no recombinants with rl), has been assembled and is being used to locate the rl gene.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Chapdelaine, P., Delahaye, S., Gauthier, E., Tremblay, R.R., Dube, J.Y. (1993). A one-hour procedure for the preparation of genomic DNA from frozen tissues. Biotechniques 14, 163–164.
Chin, H., Mock, B., Kim, H-L., Kim, H., Kozak, C.A. (1992). The gene for the dihydropyridine-sensitive calcium channel alpha2 subunit (CCHL2A) maps to the proximal region of mouse chromosome 5. Genomics 13, 1325–1327.
Cohen, D., Piekarz, R.L., Hsu, S.I-H., DePinho, R.A., Carrasco, N., Horwitz, S.B. (1991). Structural and functional analysis of the mouse mdr1b gene promoter. J. Bio. Chem. 266, 2239–2244.
Danielson, P.E., Watson, J.B., Gerendasy, D.D., Erlander, M.G., Lovenberg, T.W., de Lecea, L., Sutcliffe, J.G., Frankel, W.N. (1994). Chromosomal mapping of mouse genes expressed selectively within the central nervous system. Genomics 19, 454–461.
Dernoncourt, C., Ruelle, D., Goffinet, A.M. (1991). Estimation of genetic distances between “reeler” and nearby loci on mouse chromosome 5. Genomics 11, 1167–1169.
Dietrich, W., Katz, H., Lincoln, S.E., Shin, H-S., Friedman, J., Dracopoli, N.C., Lander, E.S. (1992). A genetic map of the mouse suitable for typing intraspecific crosses. Genetics 131, 423–447.
Dietrich, W.F., Miller, J.C., Steen, R.G., Merchant, M., Damron, D., Nahf, R., Gross, A., Joyce, D.C., Wessel, M., Dredge, R.D., Marquis, A., Stein, L.D., Goodman, N., Page, D.C., Lander, E.S. (1994). A genetic map of the mouse with 4,006 simple sequence length polymorphisms. Nature Genet. 7, 220–245.
Falconer, D.S. (1951). Two new mutants, “trembler” and “reeler”, with neurological actions in the house mouse (Mus musculus I.). J. Genet 50, 192–201.
Flaherty, L., Messer, A., Russell, L.B., Rinchik, E.M. (1992). Chlorambucil-induced mutations in mice recovered in homozygotes. Proc. Natl. Acad. Sci. USA 89, 2859–2863.
Frankel, W.N., Stoye, J.P., Taylor, B.A., Coffin, J.M. (1989a). Genetic analysis of endogenous xenotropic murine leukemia viruses: association with two common mouse mutations and the viral restriction locus Fv-1. J. Virol. 63, 1763–1774.
Frankel, W.N., Stoye, J.P., Taylor, B.A., Coffin, J.M. (1989b). Genetic identification of endogenous polytropic proviruses by using recombinant inbred mice. J. Virol. 63, 3810–3821.
Frohman, M.A., Dickinson, M.E., Hogan, B.L.M., Martin, G.R. (1993). Mapping of GBX-1 to mouse chromosome 5 and GBX-2 to mouse chromosome 1. Mouse Genome 91, 323–325.
Fukasawa, K.M., Li, W.-H., Yagi, K., Luo, C.-C., Li, S.S.-L. (1986). Molecular evolution of mammalian lactate dehydrogenase-A genes and pseudogenes: association of a mouse processed pseudogene with a B1 repetitive sequence. Mol. Biol. Evol. 3, 330–342.
Goffinet, A.M. (1984). Events governing organization of postmigratory neurons: studies on brain development in normal and reeler mice. Brain Res. Rev. 7, 261–296.
Goffinet, A.M. (1990). Determinants of nerve cell patterns during development: a review. Eur. J. Morphol. 28, 149–168.
Green, E.D., Olson, M.V. (1990). Systematic screening of yeast artificialchromosome libraries by use of the polymerase chain reaction. Proc. Natl. Acad. Sci. USA 87, 1213–1217.
Green, E.L. (1981). Genetics and Probability in Animal Breeding Experiments. (New York: Oxford University Press), pp 24–27.
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.
Hynes, R.O., Lander, A.D. (1992). Contact and adhesive specificities in the associations, migrations, and targeting of cells and axons. Cell 68, 303–322.
Joyner, A.L., Martin, G.R. (1987). En-1 and En-2, two mouse genes with sequence homology to the PitDrosophila engrailed gene: expression during embryogenesis. Genes Dev. 1, 29–38.
Kim, H-L., Kim, H., Lee, P., King, R.G., Chim, H. (1992). Rat brain expresses an alternatively spliced form of the dihydropyridine-sensitive L-type calcium channel alpha2 subunit. Proc. Natl. Acad. Sci. USA 89, 3251–3255.
Kleyn, P.W., Wang, C.H., Lien, L.L., Vitale, E., Pan, J., Ross, B.M., Grunn, A., Palmer, D.A., Warburton, D., Brzustowicz, L.M., Kunkel, L.M., Gilliam, T.C. (1993). Construction of a yeast artificial chromosome contig spanning the spinal muscular atrophy disease gene region. Proc. Natl. Acad. Sci. USA 90, 6801–6805.
Kusumi, K., Smith, J.S., Segre, J.A., Koos, D.S., Lander, E.S. (1993). Construction of a large-insert yeast artificial chromosome library of the mouse genome. Mamm. Genome 4, 391–392.
Laird, P.W., Zijderveld, A., Linders, K., Rudnicki, M.A., Jeanisch, R., Berns, A. (1991). Simplified mammalian DNA isolation procedure. Nucleic Acids Res. 19, 4293.
Love, J.M., Knight, A.M., McAleer, M.A., Todd, J.A. (1990). Towards construction of a high resolution map of the mouse genome using PCR-analysed microsatellites. Nucleic Acids Res. 18, 4123–4130.
Moran, D. (1991). Voltage-dependent-L-type Ca2+ channels participate in regulating neural crest migration and differentiation. Am. J. Anat. 192, 14–22.
Navone, N.M., Bianchi, A.B., Angel, J.M., Conti, C.J. (1992). A novel polymorphism near the mouse Int-2 locus. Mamm. Genome 3, 296–297.
Pinto-Lord, M.C., Evrard, P., Caviness, V.S., jr. (1982). Obstructed neuronal migration along radial glial fibers in the neocortex of the reeler mouse: a golgi-EM analysis. Dev. Brain Res. 4, 379–393.
Raymond, M., Gros, P. (1990). Cell-specific activity of cis-acting regulatory elements in the promoter of the mouse multidrug resistance gene mdrl. Mol. Cell. Biol. 10, 6036–6040.
Riley, J., Butler, R., Ogilvie, D., Finniear, R., Jenner, D., Powell, S., Anand, R., Smith, J.C., Markham, A.F. (1990). A novel, rapid method for the isolation of terminal sequences from yeast artificial chromosome (YAC) clones. Nucleic Acids Res 18, 2887–2890.
Rinchik, E.M., Bangham, J.W., Hunsicker, P.R., Cacheiro, N.L.A., Kwon, B.S., Jackson, I.J., Russell, L.B. (1990). Genetic and molecular analysis of chlorambucil-induced germ-line mutations in the mouse. Proc. Natl. Acad. Sci. USA 87, 1416–1420.
Rinchik, E.M., Flaherty, L., Russell, L.B. (1993). High-frequency induction of chromosomal rearrangements in mouse germ cells by the chemotherapeutic agent chlorambucil. Bioessays 15, 831–836.
Singh, G., Kaur, S., Stock, J.L., Jenkins, N.A., Gilbert, D.J., Copeland, N.G. Potter, S.S. (1991). Identification of 10 murine homeobox genes. Proc. Natl. Acad. Sci. USA 88, 10706–10710.
Smith, C.L., Kleo, S.R., Cantor, C.R. (1988). Pulsed-field gel electrophoresis and the technology of large DNA molecules. In: Genome Analysis—A Practical Approach, K.E. Davies, ed. (Washington, DC: IRL Press), pp. 41–72.
Thuring, R.W.J., Sanders, J.P.M., Borst, P. (1975). A freeze-squeeze method for recovering long DNA from agarose gels. Anal. Biochem. 66, 213–220.
Wada, K., Yokotani, N., Hunter, C., Doi, K., Wenthold, R.J., Shimasaki, S. (1992). Differential expression of two distinct forms of mRNA encoding members of a dipeptidyl aminopeptidase family. Proc. Natl. Acad. Sci. USA 89, 197–201.
Wada, K., Zimmerman, K.L., Adamson, M.C., Yokotani, N., Wenthold, R.J., Kozak, C.A., (1993). Genetic mapping of the mouse gene encoding dipeptidyl aminopeptidase-like proteins. Mamm. Genome 4, 234–237.
Whitehead Institute/MIT Center for Genome Research (1994). Genetic Map of the Mouse. Database Release 6.
Yokotani, N., Doi, K., Wenthold, R.J., Wada, K. (1993). Non-conservation of a catalytic residue in a dipeptidyl aminopeptidase IV-related protein encoded by a gene on human chromosome 7. Hum. Mol. Genet. 2, 1037–1039.
Yuasa, S., Kitoh, J., Oda, S.-i., Kawamura, K. (1993). Obstructed migration of purkinje cells in the developing cerebellum of the reeler mutant mouse. Anat. Embryol. 188, 317–329.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Montgomery, J.C., Guarníeri, M.H., Tartaglia, K.E. et al. High-resolution genetic map and YAC contig around the mouse neurological locus reeler. Mammalian Genome 5, 756–761 (1994). https://doi.org/10.1007/BF00292008
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00292008