Abstract
A novel spontaneous neurological mutation, scrambler (scm), appeared in the inbred mouse strain DC/Le (dancer) in 1991. Mice homozygous for this recessive mutation are recognized by an unstable gait and whole-body tremor. The cerebella of 30-day-old scrambler homozygotes are hypoplastic and devoid of folia; however, neither seizures nor abnormal brain wave patterns have been observed. Homozygous scrambler mutants have an ataxic gait which in the male may be a contributory factor in the failure to mate. Female homozygotes mate and breed. Life span is not reduced in either sex. Scrambler is similar to the reeler mutation in phenotype and pathology and, like reeler, probably results from defective neuronal migration. We mapped the scrambler mutation to Chromosome (Chr) 4, proving that it is distinct from the recently cloned reeler gene on Chr 5. We also determined the map position of the agrin gene, Agrn, on Chr 4, and on this basis eliminated it as a candidate for scm. Currently there is no known homology of scrambler with human lissencephalies or other human disorders caused by abnormal neuronal migration.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
D’Arcangelo, G., Meas, G.G., Chen, S.-C, Soares, H., Morgan, J.I., Curran, T. (1995). A protein related to extracellular matrix proteins deleted in the mouse mutant reeler. Nature 374, 719–723.
Davisson, M.T. (1990). The Jackson Laboratory Mouse Mutant Resource. Lab Animal 19, 23–29.
Deol, M.S., Green, M.C. (1966). Snell’s waltzer, a new mutation affecting behaviour and the inner ear of the mouse. Genet. Res. 8, 339–345.
Dietrich, W., Katz, S.E., Lincoln, H.S., Shen, J., Friedman, N.C., Dracopole, H.G., Lander, E.S. (1992). A genetic map of the mouse suitable for typing intraspecific crosses. Genetics 131, 423–447.
Doolittle, D.P., Davisson, M.T., Guidi, J.N. (1996). Catalog of mutant genes and polymorphic loci. In Genetic Variants and Strains of the Laboratory Mouse, 3rd ed., M.F. Lyon, S. Rastan, A.G. Searle, eds. (Oxford: Oxford University Press), pp. 17–854.
Green, E.L. (1985). Tables and a computer program for analyzing linkage data. Mouse News Lett. 72, 20.
Hattori, M., Adachi, H., Tsujimoto, M., Arai, H., Inoue, K. (1994). Miller-Dieker lissencephaly gene encodes a subunit of brain platelet-activating factor. Nature 370, 216–218.
Johnson, K.R., Cook, S.A., Ward-Bailey, P., Bustin, M., Davisson, M.T. (1993). Identification and genetic mapping of the murine gene and 20 related sequences encoding chromosomal protein HMG-17. Mamm. Genome 4, 83–89.
Lane, P.W., Bronson, R.T., Spencer, C.A. (1990). Rostral cerebellar malformation (rcm): a new recessive mutation on Chromosome 3 of the mouse. J. Hered. 83, 315–318.
Manly, K.F. (1993). A Macintosh program for storage and analysis of experimental genetic mapping data. Mamm. Genome 4, 303–313.
Mouse Genome Database (MGD) (1996). Mouse Genome Informatics Project, The Jackson Laboratory, Bar Harbor, Me. World Wide Web URL = http://www.informatics.jax.org/.
OMIM, On-line Mendelian Inheritance in Man, VA McKusick, available through GDB, the Human Genome Database at The Johns Hopkins University Welch Library. World Wide Web URL = http:// gdbwww.gdb.org/.
Reiner, O., Carrozzo, R., Shen, Y., Wehnert, M., Faustinella, F., Dobyns, W.B., Caskey, C.T., Ledbetter, D.H. (1993). Isolation of a Miller-Dieker lissencephaly gene containing G protein beta-subunit-like repeats. Nature 364, 717–721.
Reiner, O., Albrecht, U., Gordon, M., Chianese, K.A., Wong, C., GalGerber, O., Sapir, T., Siracusa, L.D., Buchberg, A.M., Caskey, C.T., Eichele, G. (1995). Lissencephaly gene (LIS1) expression in the CNS suggests a role in neuronal migration. J. Neurosci. 15, 3730–3738.
Rupp, F., Payan, D.G., Magill-Solc, C., Cowan, D.M., Scheller, R.H. (1991). Structure and expression of a rat agrin. Neuron 6, 811–823.
Rupp, F., Ozceiik, T., Linial, M., Peterson, K., Francke, U., Scrieller, R. (1992). Structure and chromosomal localization of the mammalian agrin gene. J. Neurosci. 12, 3535–3544.
Sakimura, K., Morita, T., Kushiya, E., Mishina, M. (1992). Primary structure and expression of the gamma 2 subunit of the glutamate receptor channel selective for kainate. Neuron 8, 267–274.
Sweet, H.O. (1991). Mouse Genome 89, 844.
Toda, T., Yoshioka, M., Nakahori, Y., Kanazawa, I., Nakamura, Y., Nakagome, Y. (1995). Genetic identity of Fukuyama-type congenital muscular dystrophy and Walker-Warburg syndrome. Ann. Neurol. 37, 99–101.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sweet, H.O., Bronson, R.T., Johnson, K.R. et al. Scrambler, a new neurological mutation of the mouse with abnormalities of neuronal migration. Mammalian Genome 7, 798–802 (1996). https://doi.org/10.1007/s003359900240
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s003359900240