Abstract
Neuromuscular degeneration, nmd, is a spontaneous autosomal recessive mutation in the mouse producing progressive hindlimb impairment caused by spinal muscular atrophy. We used an intersubspecific intercross between B6.BKs-nmd 2J/+ and Mus musculus castaneus (CAST/Ei) to map the nmd mutation to mouse Chromosome (Chr) 19 with the most likely gene order: nmd-(D19Se12, Pygm)-Cntf-Pomc2-D19Mit16-Cyp2c-Got1. nmd maps near muscle deficient, mdf, and has a very similar clinical phenotype, but allele tests and histological differences suggest that nmd is a distinct mutation at a different locus. Although closely linked, nmd recombined with the candidate genes muscle glycogen phosphorylase, Pygm, and ciliary neurotrophic factor, Cntf.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andrews, J.M. (1975). The fine structure of the cervical spinal cord, ventral root and brachial nerves in the wobbler (wr) mouse. J. Neuropathol. Exp. Neurol. 34, 12–27.
Arakawa, Y., Sendtner, M., Thoenen, H. (1990). Survival effects of ciliary neurotrophic factor (CNTF) on chick embryonic motoneurons in culture: comparison with other neurotrophic factors and cytokines. J. Neurosci. 10, 3507–3515.
Ashby, P.R., Pincon-Raymond, M., Harris, A.J. (1993). Regulation oc myogenesis in paralyzed muscles in the mouse mutants peroneal muscular atrophy and muscular dysgenesis. Dev. Biol. 156, 529–536.
Bronson, R.T., Lake, B.D., Cook, S., Taylor, S., Davisson, M.T. (1993). Motor neuron degeneration of mice is a model of neuronal ceroid fuscinosis (Batten disease). Ann. Neurol. 33, 381–385.
Chou, S.M., Fakadej, A.V. (1971). Ultrastructure of chromatolytic motor neurons and spinal anterior spinal roots in a case of Werdnig-Hoffman disease. J. Neuropathol. Exp. Neurol. 30, 368–379.
Davisson, M.T. (1990). The Jackson Laboratory mouse mutant resource. Lab. Anim. 19, 23–29.
DeLorenzo, R.J., Ruddle, F.H. (1970). Glutamate oxalate transaminase (GOT) in Mus musculus; linkage, polymorphism, and phenotypes of Got-2 and Got-1 loci. Biochem. Genet. 4, 259–273.
Dietrich, W., Katz, H., Lincoln, S.E., Shin, H.S., Fiedman, J., Dracopoli, N.C., Lander, E.S. (1992). A genetic map of the mouse suitable for typing intraspecfic crosses. Genetics 131, 423–447.
Duchen, L.W., Strich, S.J. (1968). An hereditary motor neurone disease with progressive denervation of muscle in the mouse: the mutant “wobbler”. J. Neurol. Neurosurg. Psychiatry 31, 535–542.
Fletterick, R.J., Madsen, N.B. (1980). The structures and related functions of phosphorylase a. Annu. Rev. Biochem. 49, 31–61.
GBASE (1994). The Online Genomic Database for the Mouse maintained at The Jackson Laboratory by L.J. Maltais, D.P. Doolittle, M.T. Davisson, J.N. Guidi, T.H. Roderick.
Glaser, T., Matthews, K.E., Hudson, J.W., Seth, P., Housman, D.E., Crerar, M.M. (1989). Localization of the muscle, liver, and brain glycogen phosphorylase genes on linkage maps of mouse Chromosomes 19, 12, and 2, respectively. Genomics 5, 510–521.
Hentati, A., Bejaoui, K., Pericak-Vance, M.A., Hentati, F., Hung, W.Y., Figlewicz, D.A., Ben Hamida, C., Ben Hamida, M., Brown, R.H., Siddique, T. (1992). The gene locus for one form of juvenile amyotrophic lateral sclerosis maps to chromosome 2. Neurology 42 (Suppl), 201.
Johnson, K.R., Cook, S.A., Davisson, M.T. (1992). Chromosomal localization of the murine gene and two related sequences encoding highmobility group I and Y proteins. Genomics 12, 503–509.
Jones, J.M., Albin, R.L., Feldman, E.L., Simin, K., Schuster, T.G., Dunnick, W.A., Collins, J.T., Chrisp, C.E., Taylor, B.A., Meisler, M.H. (1993). mnd2: a new mouse model of inherited motor neuron disease. Genomics 16, 669–677.
Kaupmann, K., Sendtner, M., Stöcki, K.A., Jockusch, H. (1991). The gene for ciliary neurotrophic factor (CNTF) maps to murine chromosome 19 and its expression is not affected in the hereditary motorneuron disease ‘wobbler’ of the mouse. Eur. J. Neurosci. 3, 1182–1186.
Lander, E.S., Green, P., Abrahamson, J., Barlow, A., Daly, M.J., Lincoln, S.E., Newburgh, L. (1987). MAPMAKER: an interactive computer package for constructing primary genetic linkage maps of experimental and natural populations. Genomics 1, 174–181.
Lutsep, H.L., Rodriquez, M., (1989). Ultrastructural, morphometric, and immunocytochemical study of anterior horn cells in mice with “wasted” mutation. J. Neuropathol. Exp. Neurol. 48, 519–533.
Manly, K.F. (1993). A Macintosh program for storage and analysis of experimental genetic mapping data. Mamm. Genome 4, 303–313.
Masu, Y., Wolf, E., Holtmann, B., Sendtner, M., Brem, G., Thoenen, H. (1993). Disruption of the CNTF gene results in motor neuron degeneration. Nature 365, 27–32.
Oppenheimer, D.R. (1984). Diseases of the basal ganglia, cerebellum and motor neurons. In Greenfields Neuropathology, J.H. Adams, J. Corsellis, L.W. Duchen, New York: John Wiley, pp. 699–747.
Schmalbruch, H., Skovgaard, H.-J., Bjaerg, M., Kamieniecka, Z., Kurland, L., (1991). A new mouse mutant with progressive motor neuropathy. J. Neuropathol. Exp. Neurol 50, 192–204.
Sendtner, M., Kreutzberg, G.W., Thoenen, H. (1990). Ciliary neurotrophic factor prevents the degeneration of motor neuron after axotomy. Nature 345, 440–443.
Sendtner, M., Schmalbruch, H., Stöcki, K.A., Carroll, P., Kreutzberg, G.W., Thoenen, H. (1992). Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy. Nature 358, 502–504.
Siddique, T., Figlewicz, D.A., Pericak-Vance, M.A., Haines, J.L., Rouleau, G., Jeffers, A.J., Sapp, P., Hung, W.Y., Bebout, J., McKenna-Yasek, D., Deng, G., Horvitz, H.R., Gusella, J.F., Brown, R.H., Roses, A.D., (1991). Linkage of a gene causing amyotrophic lateral sclerosis to chromosome 21 and evidence of genetic-locus heterogeneity. N. Engl. J. Med. 324, 1381–1384.
Sweet, H.O., (1983). [muscle deficient (mdf)]. Mouse News Lett. 68, 72.
Wirth, B., Voosen, B., Röhrig, D., Knapp, M., Piechaczek, B., Rudnik-Schöneborn, S., Zerres, K. (1993). Fine mapping and narrowing of the genetic interval of the spinal muscular atrophy region by linkage studies. Genomics 15, 113–118.
Woloschak, G.E., Rodriquez, M., Krco, C.J., (1987). Characterization of immunologic and neuropathologic abnormalities in wasted mice. J. Immunol. 138, 2493–2499.
Womack, J.E., MacPike, A., Meier H. (1980). Muscle deficient, a new mutation in the mouse. J. Hered. 71, 68.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cook, S.A., Johnson, K.R., Bronson, R.T. et al. Neuromuscular degeneration (nmd): a mutation on mouse Chromosome 19 that causes motor neuron degeneration. Mammalian Genome 6, 187–191 (1995). https://doi.org/10.1007/BF00293010
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00293010