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Mouse Models for Drug Discovery pp 347–393Cite as

Neuromuscular Disease Models and Analysis

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 602))

Abstract

Neuromuscular diseases can affect the survival of peripheral neurons, their axons extending to peripheral targets, their synaptic connections onto those targets, or the targets themselves. Examples include motor neuron diseases such as amyotrophic lateral sclerosis, peripheral neuropathies, such as Charcot-Marie-Tooth diseases, myasthenias, and muscular dystrophies. Characterizing these phenotypes in mouse models requires an integrated approach, examining both the nerve and the muscle histologically, anatomically, and functionally by electrophysiology. Defects observed at these levels can be related back to onset, severity, and progression, as assessed by “quality-of-life measures” including tests of gross motor performance such as gait or grip strength. This chapter describes methods for assessing neuromuscular disease models in mice, and how interpretation of these tests can be complicated by the inter-relatedness of the phenotypes.

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References

  1. Hegedus, J., Putman, C. T. and Gordon, T. (2007) Time course of preferential motor unit loss in the SOD1 G93A mouse model of amyotrophic lateral sclerosis. Neurobiol Dis 28, 154–164.

    PubMed  CAS  Google Scholar 

  2. Grohmann, K., Schuelke, M., Diers, A., Hoffmann, K., Lucke, B., Adams, C., et al. (2001) Mutations in the gene encoding immunoglobulin mu-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1. Nat Genet 29, 75–77.

    PubMed  CAS  Google Scholar 

  3. Seburn, K. L., Nangle, L. A., Cox, G. A., Schimmel, P. and Burgess, R. W. (2006) An active dominant mutation of glycyl-tRNA synthetase causes neuropathy in a Charcot-Marie-Tooth 2D mouse model. Neuron 51, 715–726.

    PubMed  CAS  Google Scholar 

  4. Court, F. A., Sherman, D. L., Pratt, T., Garry, E. M., Ribchester, R. R., Cottrell, D. F., et al. (2004) Restricted growth of Schwann cells lacking Cajal bands slows conduction in myelinated nerves. Nature 431, 191–195.

    PubMed  CAS  Google Scholar 

  5. Son, Y. J. and Thompson, W. J. (1995) Nerve sprouting in muscle is induced and guided by processes extended by Schwann cells. Neuron 14, 133–141.

    PubMed  CAS  Google Scholar 

  6. Son, Y. J. and Thompson, W. J. (1995) Schwann cell processes guide regeneration of peripheral axons. Neuron 14, 125–132.

    PubMed  CAS  Google Scholar 

  7. Enomoto, H., Araki, T., Jackman, A., Heuckeroth, R. O., Snider, W. D., Johnson, E. M., Jr., et al. (1998) GFR alpha1-deficient mice have deficits in the enteric nervous system and kidneys. Neuron 21, 317–324.

    PubMed  CAS  Google Scholar 

  8. Patton, B. L., Cunningham, J. M., Thyboll, J., Kortesmaa, J., Westerblad, H., Edstrom, L., et al. (2001) Properly formed but improperly localized synaptic specializations in the absence of laminin alpha4. Nat Neurosci 4, 597–604.

    PubMed  CAS  Google Scholar 

  9. Pun, S., Santos, A. F., Saxena, S., Xu, L. and Caroni, P. (2006) Selective vulnerability and pruning of phasic motoneuron axons in motoneuron disease alleviated by CNTF. Nat Neurosci 9, 408–419.

    PubMed  CAS  Google Scholar 

  10. Morgan, D., Munireddy, S., Alamed, J., Deleon, J., Diamond, D. M., Bickford, P., et al. (2008) Apparent behavioral benefits of tau overexpression in P301L tau transgenic mice. J Alzheimers Dis 15, 605–614.

    PubMed  CAS  Google Scholar 

  11. Stam, N. C., Nithianantharajah, J., Howard, M. L., Atkin, J. D., Cheema, S. S. and Hannan, A. J. (2008) Sex-specific behavioural effects of environmental enrichment in a transgenic mouse model of amyotrophic lateral sclerosis. Eur J Neurosci 28, 717–723.

    PubMed  Google Scholar 

  12. Turgeman, T., Hagai, Y., Huebner, K., Jassal, D. S., Anderson, J. E., Genin, O., et al. (2008) Prevention of muscle fibrosis and improvement in muscle performance in the mdx mouse by halofuginone. Neuromuscul Disord 18, 857–868.

    PubMed  Google Scholar 

  13. Bohlen, M., Cameron, A., Metten, P., Crabbe, J. C. and Wahlsten, D. (2009) Calibration of rotational acceleration for the rotarod test of rodent motor coordination. J Neurosci Methods 178, 10–14.

    Google Scholar 

  14. Rustay, N. R., Wahlsten, D. and Crabbe, J. C. (2003) Influence of task parameters on rotarod performance and sensitivity to ethanol in mice. Behav Brain Res 141, 237–249.

    PubMed  CAS  Google Scholar 

  15. Bautmans, I. and Mets, T. (2005) A fatigue resistance test for elderly persons based on grip strength: reliability and comparison with healthy young subjects. Aging Clin Exp Res 17, 217–222.

    PubMed  Google Scholar 

  16. Fernagut, P. O., Diguet, E., Labattu, B. and Tison, F. (2002) A simple method to measure stride length as an index of nigrostriatal dysfunction in mice. J Neurosci Methods 113, 123–130.

    PubMed  Google Scholar 

  17. Wooley, C. M., Sher, R. B., Kale, A., Frankel, W. N., Cox, G. A. and Seburn, K. L. (2005) Gait analysis detects early changes in transgenic SOD1(G93A) mice. Muscle Nerve 32, 43–50.

    PubMed  CAS  Google Scholar 

  18. Wooley, C. M., Xing, S., Burgess, R. W., Cox, G. A. and Seburn, K. L. (2009) Age, experience and genetic background influence treadmill walking in mice. Physiol Behav 96, 350–361.

    Google Scholar 

  19. Brooks, S. V., Faulkner, J. A. and McCubbrey, D. A. (1990) Power outputs of slow and fast skeletal muscles of mice. J Appl Physiol 68, 1282–1285.

    PubMed  CAS  Google Scholar 

  20. Seburn, K. L. and Gardiner, P. (1995) Adaptations of rat lateral gastrocnemius motor units in response to voluntary running. J Appl Physiol 78, 1673–1678.

    PubMed  CAS  Google Scholar 

  21. Lynch, G. S., Hinkle, R. T., Chamberlain, J. S., Brooks, S. V. and Faulkner, J. A. (2001) Force and power output of fast and slow skeletal muscles from mdx mice 6-28 months old. J Physiol 535, 591–600.

    PubMed  CAS  Google Scholar 

  22. Brooks, S. V. and Faulkner, J. A. (1988) Contractile properties of skeletal muscles from young, adult and aged mice. J Physiol 404, 71–82.

    PubMed  CAS  Google Scholar 

  23. Grange, R. W., Gainer, T. G., Marschner, K. M., Talmadge, R. J. and Stull, J. T. (2002) Fast-twitch skeletal muscles of dystrophic mouse pups are resistant to injury from acute mechanical stress. Am J Physiol Cell Physiol 283, C1090–1101.

    PubMed  CAS  Google Scholar 

  24. Belluardo, N., Westerblad, H., Mudo, G., Casabona, A., Bruton, J., Caniglia, G., et al. (2001) Neuromuscular junction disassembly and muscle fatigue in mice lacking neurotrophin-4. Mol Cell Neurosci 18, 56–67.

    PubMed  CAS  Google Scholar 

  25. Danieli-Betto, D., Esposito, A., Germinario, E., Sandona, D., Martinello, T., Jakubiec-Puka, A., et al. (2005) Deficiency of alpha-sarcoglycan differently affects fast- and slow-twitch skeletal muscles. Am J Physiol Regul Integr Comp Physiol 289, R1328–1337.

    PubMed  CAS  Google Scholar 

  26. Grange, R. W., Meeson, A., Chin, E., Lau, K. S., Stull, J. T., Shelton, J. M., et al. (2001) Functional and molecular adaptations in skeletal muscle of myoglobin-mutant mice. Am J Physiol Cell Physiol 281, C1487–1494.

    PubMed  CAS  Google Scholar 

  27. Parry, D. J. and Desypris, G. (1985) Fatiguability and oxidative capacity of forelimb and hind limb muscles of dystrophic mice. Exp Neurol 87, 358–368.

    PubMed  CAS  Google Scholar 

  28. Swallow, J. G., Garland, T., Jr., Carter, P. A., Zhan, W. Z. and Sieck, G. C. (1998) Effects of voluntary activity and genetic selection on aerobic capacity in house mice (Mus domesticus). J Appl Physiol 84, 69–76.

    PubMed  CAS  Google Scholar 

  29. Shefner, J. M. (2001) Motor unit number estimation in human neurological diseases and animal models. Clin Neurophysiol 112, 955–964.

    PubMed  CAS  Google Scholar 

  30. McComas, A. J., Fawcett, P. R., Campbell, M. J. and Sica, R. E. (1971) Electrophysiological estimation of the number of motor units within a human muscle. J Neurol Neurosurg Psychiatry 34, 121–131.

    PubMed  CAS  Google Scholar 

  31. Major, L. A., Hegedus, J., Weber, D. J., Gordon, T. and Jones, K. E. (2007) Method for counting motor units in mice and validation using a mathematical model. J Neurophysiol 97, 1846–1856.

    PubMed  Google Scholar 

  32. Ebels, E. J. (1975) Dark neurons: a significant artifact: the influence of the maturational state of neurons on the occurrence of the phenomenon. Acta Neuropathol 33, 271–273.

    PubMed  CAS  Google Scholar 

  33. Garman, R. H. (1990) Artifacts in routinely immersion fixed nervous tissue. Toxicol Pathol 18, 149–153.

    PubMed  CAS  Google Scholar 

  34. Jortner, B. S. (2006) The return of the dark neuron. A histological artifact complicating contemporary neurotoxicologic evaluation. Neurotoxicology 27, 628–634.

    PubMed  CAS  Google Scholar 

  35. Schrèoder, J. M. (2001) Pathology of peripheral nerves: an atlas of structural and molecular pathological changes, Springer, Berlin/New York.

    Google Scholar 

  36. Emery, A. E. H. (1998) Neuromuscular disorders: clinical and molecular genetics, John Wiley, Chichester/New York.

    Google Scholar 

  37. Dyck, P. J. and Thomas, P. K. (2005) Peripheral neuropathy, 4th ed. Elsevier Saunders, Philadelphia, PA.

    Google Scholar 

  38. Engel, A. and Franzini-Armstrong, C. (2004) Myology: basic and clinical, 3rd ed. McGraw-Hill, Medical Pub. Division,INTbreak; New York.

    Google Scholar 

  39. Maddatu, T. P., Garvey, S. M., Schroeder, D. G., Hampton, T. G. and Cox, G. A. (2004) Transgenic rescue of neurogenic atrophy in the nmd mouse reveals a role for Ighmbp2 in dilated cardiomyopathy. Hum Mol Genet 13, 1105–1115.

    PubMed  CAS  Google Scholar 

  40. Hershkovitz, E., Rozin, I., Limony, Y., Golan, H., Hadad, N., Gorodischer, R., et al. (2007) Hypoparathyroidism, retardation, and dysmorphism syndrome: impaired early growth and increased susceptibility to severe infections due to hyposplenism and impaired polymorphonuclear cell functions. Pediatr Res 62, 505–509.

    PubMed  Google Scholar 

  41. Noakes, P. G., Miner, J. H., Gautam, M., Cunningham, J. M., Sanes, J. R. and Merlie, J. P. (1995) The renal glomerulus of mice lacking s-laminin/laminin b2: nephrosis despite molecular compensation by laminin b1. Nat Genet 10, 400–406.

    PubMed  CAS  Google Scholar 

  42. Zhai, R. G., Cao, Y., Hiesinger, P. R., Zhou, Y., Mehta, S. Q., Schulze, K. L., et al. (2006) Drosophila NMNAT maintains neural integrity independent of its NAD synthesis activity. PLoS Biol 4, e416.

    PubMed  Google Scholar 

  43. Zhai, R. G., Zhang, F., Hiesinger, P. R., Cao, Y., Haueter, C. M. and Bellen, H. J. (2008) NAD synthase NMNAT acts as a chaperone to protect against neurodegeneration. Nature 452, 887–891.

    PubMed  CAS  Google Scholar 

  44. Press, C. and Milbrandt, J. (2008) Nmnat delays axonal degeneration caused by mitochondrial and oxidative stress. J Neurosci 28, 4861–4871.

    PubMed  CAS  Google Scholar 

  45. Maddatu, T. P., Garvey, S. M., Schroeder, D. G., Zhang, W., Kim, S. Y., et al. (2005) Dilated cardiomyopathy in the nmd mouse: transgenic rescue and QTLs that improve cardiac function and survival. Hum Mol Genet 14, 3179–3189.

    Google Scholar 

  46. Grohmann, K., Schuelke, M., Diers, A., Hoffmann, K., Lucke, B., Adams, C., et al. (2001) Mutations in the gene encoding immunoglobulin μ-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1. Nat Genet 29, 75–77.

    PubMed  CAS  Google Scholar 

  47. Cox, G. A., Mahaffey, C. L. and Frankel, W. N. (1998) Identification of the mouse neuromuscular degeneration gene and mapping of a second site suppressor allele. Neuron 21, 1327–1337.

    PubMed  CAS  Google Scholar 

  48. Monani, U. R., Pastore, M. T., Gavrilina, T. O., Jablonka, S., Le, T. T., Andreassi, C., et al. (2003) A transgene carrying an A2G missense mutation in the SMN gene modulates phenotypic severity in mice with severe (type I) spinal muscular atrophy. J Cell Biol 160, 41–52.

    PubMed  CAS  Google Scholar 

  49. Le, T. T., Pham, L. T., Butchbach, M. E., Zhang, H. L., Monani, U. R., Coovert, D. D., et al. (2005) SMN Delta 7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN. Hum Mol Genet 14, 845–857.

    PubMed  CAS  Google Scholar 

  50. Monani, U. R., Sendtner, M., Coovert, D. D., Parsons, D. W., Andreassi, C., Le, T. T., et al. (2000) The human centromeric survival motor neuron gene (SMN2) rescues embryonic lethality in Smn(-/-) mice and results in a mouse with spinal muscular atrophy. Hum Mol Genet 9, 333–339.

    PubMed  CAS  Google Scholar 

  51. Schrank, B., Gotz, R., Gunnersen, J. M., Ure, J. M., Toyka, K. V., Smith, A. G., et al. (1997) Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos. Proc Natl Acad Sci U S A 94, 9920–9925.

    PubMed  CAS  Google Scholar 

  52. Martin, N., Jaubert, J., Gounon, P., Salido, E., Haase, G., Szatanik, M., et al. (2002) A missense mutation in Tbce causes progressive motor neuronopathy in mice. Nat Genet 32, 443–447.

    PubMed  CAS  Google Scholar 

  53. Bommel, H., Xie, G., Rossoll, W., Wiese, S., Jablonka, S., Boehm, T., et al. (2002) Missense mutation in the tubulin-specific chaperone E (Tbce) gene in the mouse mutant progressive motor neuronopathy, a model of human motoneuron disease. J Cell Biol 159, 563–569.

    PubMed  CAS  Google Scholar 

  54. Puls, I., Jonnakuty, C., LaMonte, B. H., Holzbaur, E. L., Tokito, M., Mann, E., et al. (2003) Mutant dynactin in motor neuron disease. Nat Genet 33, 455–456.

    PubMed  CAS  Google Scholar 

  55. Chevalier-Larsen, E. S., Wallace, K. E., Pennise, C. R. and Holzbaur, E. L. (2008) Lysosomal proliferation and distal degeneration in motor neurons expressing the G59S mutation in the p150Glued subunit of dynactin. Hum Mol Genet 17, 1946–1955.

    PubMed  CAS  Google Scholar 

  56. Lai, C., Lin, X., Chandran, J., Shim, H., Yang, W. J. and Cai, H. (2007) The G59S mutation in p150(glued) causes dysfunction of dynactin in mice. J Neurosci 27, 13982–13990.

    PubMed  CAS  Google Scholar 

  57. LaMonte, B. H., Wallace, K. E., Holloway, B. A., Shelly, S. S., Ascano, J., Tokito, M., et al. (2002) Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration. Neuron 34, 715–727.

    PubMed  CAS  Google Scholar 

  58. Ripps, M. E., Huntley, G. W., Hof, P. R., Morrison, J. H. and Gordon, J. W. (1995) Transgenic mice expressing an altered murine superoxide dismutase gene provide an animal model of amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 92, 689–693.

    PubMed  CAS  Google Scholar 

  59. Kunst, C. B., Messer, L., Gordon, J., Haines, J. and Patterson, D. (2000) Genetic mapping of a mouse modifier gene that can prevent ALS onset. Genomics 70, 181–189.

    PubMed  CAS  Google Scholar 

  60. Bruijn, L. I., Becher, M. W., Lee, M. K., Anderson, K. L., Jenkins, N. A., Copeland, N. G., et al. (1997) ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron 18, 327–338.

    PubMed  CAS  Google Scholar 

  61. Wang, J., Xu, G., Gonzales, V., Coonfield, M., Fromholt, D., Copeland, N. G., et al. (2002) Fibrillar inclusions and motor neuron degeneration in transgenic mice expressing superoxide dismutase 1 with a disrupted copper-binding site. Neurobiol Dis 10, 128–138.

    PubMed  CAS  Google Scholar 

  62. Wong, P. C., Pardo, C. A., Borchelt, D. R., Lee, M. K., Copeland, N. G., Jenkins, N. A., et al. (1995) An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron 14, 1105–1116.

    PubMed  CAS  Google Scholar 

  63. Gurney, M. E., Pu, H., Chiu, A. Y., Dal Canto, M. C., Polchow, C. Y., Alexander, D. D., et al. (1994) Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 264, 1772–1775.

    PubMed  CAS  Google Scholar 

  64. Heiman-Patterson, T. D., Deitch, J. S., Blankenhorn, E. P., Erwin, K. L., Perreault, M. J., Alexander, B. K., et al. (2005) Background and gender effects on survival in the TgN(SOD1-G93A)1Gur mouse model of ALS. J Neurol Sci 236, 1–7.

    PubMed  CAS  Google Scholar 

  65. Messer, A. and Flaherty, L. (1986) Autosomal dominance in a late-onset motor neuron disease in the mouse. J Neurogenet 3, 345–355.

    PubMed  CAS  Google Scholar 

  66. Bronson, R. T., Lake, B. D., Cook, S., Taylor, S. and Davisson, M. T. (1993) Motor neuron degeneration of mice is a model of neuronal ceroid lipofuscinosis (Batten’s disease). Ann Neurol 33, 381–385.

    PubMed  CAS  Google Scholar 

  67. Ranta, S., Zhang, Y., Ross, B., Lonka, L., Takkunen, E., Messer, A., et al. (1999) The neuronal ceroid lipofuscinoses in human EPMR and mnd mutant mice are associated with mutations in CLN8. Nat Genet 23, 233–236.

    PubMed  CAS  Google Scholar 

  68. Hafezparast, M., Klocke, R., Ruhrberg, C., Marquardt, A., Ahmad-Annuar, A., Bowen, S., et al. (2003) Mutations in dynein link motor neuron degeneration to defects in retrograde transport. Science 300, 808–812.

    PubMed  CAS  Google Scholar 

  69. Chen, X. J., Levedakou, E. N., Millen, K. J., Wollmann, R. L., Soliven, B. and Popko, B. (2007) Proprioceptive sensory neuropathy in mice with a mutation in the cytoplasmic Dynein heavy chain 1 gene. J Neurosci 27, 14515–14524.

    PubMed  CAS  Google Scholar 

  70. Ilieva, H. S., Yamanaka, K., Malkmus, S., Kakinohana, O., Yaksh, T., Marsala, M., et al. (2008) Mutant dynein (Loa) triggers proprioceptive axon loss that extends survival only in the SOD1 ALS model with highest motor neuron death. Proc Natl Acad Sci U S A 105, 12599–12604.

    PubMed  CAS  Google Scholar 

  71. Chow, C. Y., Landers, J. E., Bergren, S. K., Sapp, P. C., Grant, A. E., Jones, J. M., et al. (2009) Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS. Am J Hum Genet 84, 85–88.

    PubMed  CAS  Google Scholar 

  72. Chow, C. Y., Zhang, Y., Dowling, J. J., Jin, N., Adamska, M., Shiga, K., et al. (2007) Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J. Nature 448, 68–72.

    PubMed  CAS  Google Scholar 

  73. Zhang, X., Chow, C. Y., Sahenk, Z., Shy, M. E., Meisler, M. H. and Li, J. (2008) Mutation of FIG4 causes a rapidly progressive, asymmetric neuronal degeneration. Brain 131, 1990–2001.

    PubMed  Google Scholar 

  74. Schmitt-John, T., Drepper, C., Mussmann, A., Hahn, P., Kuhlmann, M., Thiel, C., et al. (2005) Mutation of Vps54 causes motor neuron disease and defective spermiogenesis in the wobbler mouse. Nat Genet 37, 1213–1215.

    PubMed  CAS  Google Scholar 

  75. Suter, U., Welcher, A. A., Ozcelik, T., Snipes, G. J., Kosaras, B., Francke, U., et al. (1992) Trembler mouse carries a point mutation in a myelin gene. Nature 356, 241–244.

    PubMed  CAS  Google Scholar 

  76. Giese, K. P., Martini, R., Lemke, G., Soriano, P. and Schachner, M. (1992) Mouse P0 gene disruption leads to hypomyelination, abnormal expression of recognition molecules, and degeneration of myelin and axons. Cell 71, 565–576.

    PubMed  CAS  Google Scholar 

  77. Wrabetz, L., Feltri, M. L., Quattrini, A., Imperiale, D., Previtali, S., D’Antonio, M., et al. (2000) P(0) glycoprotein overexpression causes congenital hypomyelination of peripheral nerves. J Cell Biol 148, 1021–1034.

    PubMed  CAS  Google Scholar 

  78. Wrabetz, L., D’Antonio, M., Pennuto, M., Dati, G., Tinelli, E., Fratta, P., et al. (2006) Different intracellular pathomechanisms produce diverse Myelin Protein Zero neuropathies in transgenic mice. J Neurosci 26, 2358–2368.

    PubMed  CAS  Google Scholar 

  79. Le, N., Nagarajan, R., Wang, J. Y., Araki, T., Schmidt, R. E. and Milbrandt, J. (2005) Analysis of congenital hypomyelinating Egr2Lo/Lo nerves identifies Sox2 as an inhibitor of Schwann cell differentiation and myelination. Proc Natl Acad Sci U S A 102, 2596–2601.

    PubMed  CAS  Google Scholar 

  80. Topilko, P., Schneider-Maunoury, S., Levi, G., Baron-Van Evercooren, A., Chennoufi, A. B., Seitanidou, T., et al. (1994) Krox-20 controls myelination in the peripheral nervous system. Nature 371, 796–799.

    PubMed  CAS  Google Scholar 

  81. Nelles, E., Butzler, C., Jung, D., Temme, A., Gabriel, H. D., Dahl, U., et al. (1996) Defective propagation of signals generated by sympathetic nerve stimulation in the liver of connexin32-deficient mice. Proc Natl Acad Sci U S A 93, 9565–9570.

    PubMed  CAS  Google Scholar 

  82. Anzini, P., Neuberg, D. H., Schachner, M., Nelles, E., Willecke, K., Zielasek, J., et al. (1997) Structural abnormalities and deficient maintenance of peripheral nerve myelin in mice lacking the gap junction protein connexin 32. J Neurosci 17, 4545–4551.

    PubMed  CAS  Google Scholar 

  83. Jeng, L. J., Balice-Gordon, R. J., Messing, A., Fischbeck, K. H. and Scherer, S. S. (2006) The effects of a dominant connexin 32 mutant in myelinating Schwann cells. Mol Cell Neurosci 32, 283–298.

    PubMed  CAS  Google Scholar 

  84. Detmer, S. A., Vande Velde, C., Cleveland, D. W. and Chan, D. C. (2008) Hindlimb gait defects due to motor axon loss and reduced distal muscles in a transgenic mouse model of Charcot-Marie-Tooth type 2A. Hum Mol Genet 17, 367–375.

    PubMed  CAS  Google Scholar 

  85. Lee, M. K., Marszalek, J. R. and Cleveland, D. W. (1994) A mutant neurofilament subunit causes massive, selective motor neuron death: implications for the pathogenesis of human motor neuron disease. Neuron 13, 975–988.

    PubMed  CAS  Google Scholar 

  86. Zhu, Q., Couillard-Despres, S. and Julien, J. P. (1997) Delayed maturation of regenerating myelinated axons in mice lacking neurofilaments. Exp Neurol 148, 299–316.

    PubMed  CAS  Google Scholar 

  87. Huang, L., Min, J. N., Masters, S., Mivechi, N. F. and Moskophidis, D. (2007) Insights into function and regulation of small heat shock protein 25 (HSPB1) in a mouse model with targeted gene disruption. Genesis 45, 487–501.

    PubMed  CAS  Google Scholar 

  88. Gillespie, C. S., Sherman, D. L., Fleetwood-Walker, S. M., Cottrell, D. F., Tait, S., Garry, E. M., et al. (2000) Peripheral demyelination and neuropathic pain behavior in periaxin-deficient mice. Neuron 26, 523–531.

    PubMed  CAS  Google Scholar 

  89. Brandon, E. P., Lin, W., D’Amour, K. A., Pizzo, D. P., Dominguez, B., Sugiura, Y., et al. (2003) Aberrant patterning of neuromuscular synapses in choline acetyltransferase-deficient mice. J Neurosci 23, 539–549.

    PubMed  CAS  Google Scholar 

  90. Misgeld, T., Burgess, R. W., Lewis, R. M., Cunningham, J. M., Lichtman, J. W. and Sanes, J. R. (2002) Roles of neurotransmitter in synapse formation. Development of neuromuscular junctions lacking choline acetyltransferase. Neuron 36, 635–648.

    PubMed  CAS  Google Scholar 

  91. Buffelli, M., Burgess, R. W., Feng, G., Lobe, C. G., Lichtman, J. W. and Sanes, J. R. (2003) Genetic evidence that relative synaptic efficacy biases the outcome of synaptic competition. Nature 424, 430–434.

    PubMed  CAS  Google Scholar 

  92. Prado, V. F., Martins-Silva, C., de Castro, B. M., Lima, R. F., Barros, D. M., Amaral, E., et al. (2006) Mice deficient for the vesicular acetylcholine transporter are myasthenic and have deficits in object and social recognition. Neuron 51, 601–612.

    PubMed  CAS  Google Scholar 

  93. Feng, G., Krejci, E., Molgo, J., Cunningham, J. M., Massoulie, J. and Sanes, J. R. (1999) Genetic analysis of collagen Q: roles in acetylcholinesterase and butyrylcholinesterase assembly and in synaptic structure and function. J Cell Biol 144, 1349–1360.

    PubMed  CAS  Google Scholar 

  94. Adler, M., Manley, H. A., Purcell, A. L., Deshpande, S. S., Hamilton, T. A., Kan, R. K., et al. (2004) Reduced acetylcholine receptor density, morphological remodeling, and butyrylcholinesterase activity can sustain muscle function in acetylcholinesterase knockout mice. Muscle Nerve 30, 317–327.

    PubMed  CAS  Google Scholar 

  95. Mesulam, M. M., Guillozet, A., Shaw, P., Levey, A., Duysen, E. G. and Lockridge, O. (2002) Acetylcholinesterase knockouts establish central cholinergic pathways and can use butyrylcholinesterase to hydrolyze acetylcholine. Neuroscience 110, 627–639.

    PubMed  CAS  Google Scholar 

  96. Burgess, R. W., Nguyen, Q. T., Son, Y. J., Lichtman, J. W. and Sanes, J. R. (1999) Alternatively spliced isoforms of nerve- and muscle-derived agrin: their roles at the neuromuscular junction. Neuron 23, 33–44.

    PubMed  CAS  Google Scholar 

  97. Burgess, R. W., Skarnes, W. C. and Sanes, J. R. (2000) Agrin isoforms with distinct amino termini: differential expression, localization, and function. J Cell Biol 151, 41–52.

    PubMed  CAS  Google Scholar 

  98. Lin, W., Burgess, R. W., Dominguez, B., Pfaff, S. L., Sanes, J. R. and Lee, K. F. (2001) Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse. Nature 410, 1057–1064.

    PubMed  CAS  Google Scholar 

  99. Harvey, S. J., Jarad, G., Cunningham, J., Rops, A. L., van der Vlag, J., Berden, J. H., et al. (2007) Disruption of glomerular basement membrane charge through podocyte-specific mutation of agrin does not alter glomerular permselectivity. Am J Pathol 171, 139–152.

    Google Scholar 

  100. Gautam, M., Noakes, P. G., Moscoso, L., Rupp, F., Scheller, R. H., Merlie, J. P., et al. (1996) Defective neuromuscular synaptogenesis in agrin-deficient mutant mice. Cell 85, 525–535.

    PubMed  CAS  Google Scholar 

  101. DeChiara, T. M., Bowen, D. C., Valenzuela, D. M., Simmons, M. V., Poueymirou, W. T., Thomas, S., et al. (1996) The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo. Cell 85, 501–512.

    PubMed  CAS  Google Scholar 

  102. Weatherbee, S. D., Anderson, K. V. and Niswander, L. A. (2006) LDL-receptor-related protein 4 is crucial for formation of the neuromuscular junction. Development 133, 4993–5000.

    PubMed  CAS  Google Scholar 

  103. Gautam, M., Noakes, P. G., Mudd, J., Nichol, M., Chu, G. C., Sanes, J. R.,et al. (1995) Failure of postsynaptic specialization to develop at neuromuscular junctions of rapsyn-deficient mice. Nature 377, 232–236.

    PubMed  CAS  Google Scholar 

  104. Okada, K., Inoue, A., Okada, M., Murata, Y., Kakuta, S., Jigami, T., et al. (2006) The muscle protein Dok-7 is essential for neuromuscular synaptogenesis. Science 312, 1802–1805.

    PubMed  CAS  Google Scholar 

  105. Noakes, P. G., Gautam, M., Mudd, J., Sanes, J. R. and Merlie, J. P. (1995) Aberrant differentiation of neuromuscular junctions in mice lacking s-laminin/laminin beta 2. Nature 374, 258–262.

    PubMed  CAS  Google Scholar 

  106. Friese, M. B., Blagden, C. S. and Burden, S. J. (2007) Synaptic differentiation is defective in mice lacking acetylcholine receptor beta-subunit tyrosine phosphorylation. Development 134, 4167–4176.

    PubMed  CAS  Google Scholar 

  107. Missias, A. C., Mudd, J., Cunningham, J. M., Steinbach, J. H., Merlie, J. P. and Sanes, J. R. (1997) Deficient development and maintenance of postsynaptic specializations in mutant mice lacking an ’adult’ acetylcholine receptor subunit. Development 124, 5075–5086.

    PubMed  CAS  Google Scholar 

  108. Witzemann, V., Schwarz, H., Koenen, M., Berberich, C., Villarroel, A., Wernig, A., et al. (1996) Acetylcholine receptor epsilon-subunit deletion causes muscle weakness and atrophy in juvenile and adult mice. Proc Natl Acad Sci USA 93, 13286–13291.

    PubMed  CAS  Google Scholar 

  109. Takahashi, M., Kubo, T., Mizoguchi, A., Carlson, C. G., Endo, K. and Ohnishi, K. (2002) Spontaneous muscle action potentials fail to develop without fetal-type acetylcholine receptors. EMBO Rep 3, 674–681.

    PubMed  CAS  Google Scholar 

  110. Koenen, M., Peter, C., Villarroel, A., Witzemann, V. and Sakmann, B. (2005) Acetylcholine receptor channel subtype directs the innervation pattern of skeletal muscle. EMBO Rep 6, 570–576.

    PubMed  CAS  Google Scholar 

  111. Liu, Y., Padgett, D., Takahashi, M., Li, H., Sayeed, A., Teichert, R. W., et al. (2008) Essential roles of the acetylcholine receptor gamma-subunit in neuromuscular synaptic patterning. Development 135, 1957–1967.

    PubMed  CAS  Google Scholar 

  112. Sicinski, P., Geng, Y., Ryder Cook, A. S., Barnard, E. A., Darlison, M. G. and Barnard, P. J. (1989) The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. Science 244, 1578–1580.

    PubMed  CAS  Google Scholar 

  113. Chapman, V. M., Miller, D. R., Armstrong, D. and Caskey, C. T. (1989) Recovery of induced mutations for X chromosome-linked muscular dystrophy in mice. Proc Natl Acad Sci U S Am 86, 1292–1296.

    CAS  Google Scholar 

  114. Danko, I., Chapman, V. and Wolff, J. A. (1992) The frequency of revertants in mdx mouse genetic models for Duchenne muscular dystrophy. Pediatr Res 32, 128–131.

    PubMed  CAS  Google Scholar 

  115. Cox, G. A., Phelps, S. F., Chapman, V. M. and Chamberlain, J. S. (1993) New mdx mutation disrupts expression of muscle and nonmuscle isoforms of dystrophin. Nature Genetics 4, 87–93.

    PubMed  CAS  Google Scholar 

  116. Im, W. B., Phelps, S. F., Copen, E. H., Adams, E. G., Slightom, J. L. and Chamberlain, J. S. (1996) Differential expression of dystrophin isoforms in strains of mdx mice with different mutations. Hum Mol Genet 5, 1149–1153.

    PubMed  CAS  Google Scholar 

  117. Araki, E., Nakamura, K., Nakao, K., Kameya, S., Kobayashi, O., Nonaka, I., et al. (1997) Targeted disruption of exon 52 in the mouse dystrophin gene induced muscle degeneration similar to that observed in Duchenne muscular dystrophy. Biochem Biophys Res Commun 238, 492–497.

    PubMed  CAS  Google Scholar 

  118. Kudoh, H., Ikeda, H., Kakitani, M., Ueda, A., Hayasaka, M., Tomizuka, K., et al. (2005) A new model mouse for Duchenne muscular dystrophy produced by 2.4 Mb deletion of dystrophin gene using Cre-loxP recombination system. Biochem Biophys Res Commun 328, 507–516.

    PubMed  CAS  Google Scholar 

  119. Grewal, P. K., Holzfeind, P. J., Bittner, R. E. and Hewitt, J. E. (2001) Mutant glycosyltransferase and altered glycosylation of alpha-dystroglycan in the myodystrophy mouse. Nat Genet 28, 151–154.

    PubMed  CAS  Google Scholar 

  120. Lee, Y., Kameya, S., Cox, G. A., Hsu, J., Hicks, W., Maddatu, T. P., et al. (2005) Ocular abnormalities in Large(myd) and Large(vls) mice, spontaneous models for muscle, eye, and brain diseases. Mol Cell Neurosci 30, 160–172.

    PubMed  CAS  Google Scholar 

  121. Kuang, W., Xu, H., Vachon, P. H., Liu, L., Loechel, F., Wewer, U. M., et al. (1998) Merosin-deficient congenital muscular dystrophy. Partial genetic correction in two mouse models. J Clin Invest 102, 844–852.

    PubMed  CAS  Google Scholar 

  122. Michelson, A. M., Russell, E. S. and Harman, P. J. (1955) Dystrophia muscularis: a hereditary primary myopathy in the house mouse. Proc Natl Acad Sci U S A 12, 1079–1084.

    Google Scholar 

  123. Miyagoe, Y., Hanaoka, K., Nonaka, I., Hayasaka, M., Nabeshima, Y., Arahata, K., et al. (1997) Laminin alpha2 chain-null mutant mice by targeted disruption of the Lama2 gene: a new model of merosin (laminin 2)-deficient congenital muscular dystrophy. FEBS Lett 415, 33–39.

    PubMed  CAS  Google Scholar 

  124. Patton, B. L., Wang, B., Tarumi, Y. S., Seburn, K. L. and Burgess, R. W. (2008) A single point mutation in the LN domain of LAMA2 causes muscular dystrophy and peripheral amyelination. J Cell Sci 121, 1593–1604.

    PubMed  CAS  Google Scholar 

  125. Sunada, Y., Bernier, S. M., Utani, A., Yamada, Y. and Campbell, K. P. (1995) Identification of a novel mutant transcript of laminin a2 chain gene responsible for muscular dystrophy and dysmyelination in dy2J mice. Hum Mol Genet 4, 1055–1061.

    PubMed  CAS  Google Scholar 

  126. Bittner, R. E., Anderson, L. V., Burkhardt, E., Bashir, R., Vafiadaki, E., Ivanova, S., et al. (1999) Dysferlin deletion in SJL mice (SJL-Dysf) defines a natural model for limb girdle muscular dystrophy 2B. Nat Genet 23, 141–142.

    PubMed  CAS  Google Scholar 

  127. Bansal, D., Miyake, K., Vogel, S. S., Groh, S., Chen, C. C., Williamson, R., et al. (2003) Defective membrane repair in dysferlin-deficient muscular dystrophy. Nature 423, 168–172.

    PubMed  CAS  Google Scholar 

  128. Ho, M., Post, C. M., Donahue, L. R., Lidov, H. G., Bronson, R. T., Goolsby, H., et al. (2004) Disruption of muscle membrane and phenotype divergence in two novel mouse models of dysferlin deficiency. Hum Mol Genet 13, 1999–2010.

    PubMed  CAS  Google Scholar 

  129. Grady, R. M., Grange, R. W., Lau, K. S., Maimone, M. M., Nichol, M. C., Stull, J. T., et al. (1999) Role for alpha-dystrobrevin in the pathogenesis of dystrophin-dependent muscular dystrophies. Nat Cell Biol 1, 215–220.

    PubMed  CAS  Google Scholar 

  130. Bonaldo, P., Braghetta, P., Zanetti, M., Piccolo, S., Volpin, D. and Bressan, G. M. (1998) Collagen VI deficiency induces early onset myopathy in the mouse: an animal model for Bethlem myopathy. Hum Mol Genet 7, 2135–2140.

    PubMed  CAS  Google Scholar 

  131. Irwin, W. A., Bergamin, N., Sabatelli, P., Reggiani, C., Megighian, A., Merlini, L., et al. (2003) Mitochondrial dysfunction and apoptosis in myopathic mice with collagen VI deficiency. Nat Genet 35, 367–371.

    PubMed  CAS  Google Scholar 

  132. Eklund, L., Piuhola, J., Komulainen, J., Sormunen, R., Ongvarrasopone, C., Fassler, R., et al. (2001) Lack of type XV collagen causes a skeletal myopathy and cardiovascular defects in mice. Proc Natl Acad Sci U S A 98, 1194–1199.

    PubMed  CAS  Google Scholar 

  133. Galbiati, F., Engelman, J. A., Volonte, D., Zhang, X. L., Minetti, C., Li, M., et al. (2001) Caveolin-3 null mice show a loss of caveolae, changes in the microdomain distribution of the dystrophin-glycoprotein complex, and t-tubule abnormalities. J Biol Chem 276, 21425–21433.

    PubMed  CAS  Google Scholar 

  134. Crawford, K., Flick, R., Close, L., Shelly, D., Paul, R., Bove, K., et al. (2002) Mice lacking skeletal muscle actin show reduced muscle strength and growth deficits and die during the neonatal period. Mol Cell Biol 22, 5887–5896.

    PubMed  CAS  Google Scholar 

  135. Ilkovski, B., Cooper, S. T., Nowak, K., Ryan, M. M., Yang, N., Schnell, C., et al. (2001) Nemaline myopathy caused by mutations in the muscle alpha-skeletal-actin gene. Am J Hum Genet 68, 1333–1343.

    PubMed  CAS  Google Scholar 

  136. Garvey, S. M., Rajan, C., Lerner, A. P., Frankel, W. N. and Cox, G. A. (2002) The muscular dystrophy with myositis (mdm) mouse mutation disrupts a skeletal muscle-specific domain of titin. Genomics 79, 146–149.

    PubMed  CAS  Google Scholar 

  137. Gotthardt, M., Hammer, R. E., Hubner, N., Monti, J., Witt, C. C., McNabb, M., et al. (2003) Conditional expression of mutant M-line titins results in cardiomyopathy with altered sarcomere structure. J Biol Chem 278, 6059–6065.

    PubMed  CAS  Google Scholar 

  138. May, S. R., Stewart, N. J., Chang, W. and Peterson, A. S. (2004) A Titin mutation defines roles for circulation in endothelial morphogenesis. Dev Biol 270, 31–46.

    PubMed  CAS  Google Scholar 

  139. Brady, J. P., Garland, D. L., Green, D. E., Tamm, E. R., Giblin, F. J. and Wawrousek, E. F. (2001) AlphaB-crystallin in lens development and muscle integrity: a gene knockout approach. Invest Ophthalmol Vis Sci 42, 2924–2934.

    PubMed  CAS  Google Scholar 

  140. Homma, S., Iwasaki, M., Shelton, G. D., Engvall, E., Reed, J. C. and Takayama, S. (2006) BAG3 deficiency results in fulminant myopathy and early lethality. Am J Pathol 169, 761–773.

    PubMed  CAS  Google Scholar 

  141. Selcen, D., Muntoni, F., Burton, B. K., Pegoraro, E., Sewry, C., Bite, A. V., et al. (2009) Mutation in BAG3 causes severe dominant childhood muscular dystrophy. Ann Neurol 65, 83–89.

    Google Scholar 

  142. Li, Z., Colucci-Guyon, E., Pincon-Raymond, M., Mericskay, M., Pournin, S., Paulin, D., et al. (1996) Cardiovascular lesions and skeletal myopathy in mice lacking desmin. Dev Biol 175, 362–366.

    PubMed  CAS  Google Scholar 

  143. Milner, D. J., Weitzer, G., Tran, D., Bradley, A. and Capetanaki, Y. (1996) Disruption of muscle architecture and myocardial degeneration in mice lacking desmin. J Cell Biol 134, 1255–1270.

    PubMed  CAS  Google Scholar 

  144. Thornell, L., Carlsson, L., Li, Z., Mericskay, M. and Paulin, D. (1997) Null mutation in the desmin gene gives rise to a cardiomyopathy. J Mol Cell Cardiol 29, 2107–2124.

    PubMed  CAS  Google Scholar 

  145. Moza, M., Mologni, L., Trokovic, R., Faulkner, G., Partanen, J. and Carpen, O. (2007) Targeted deletion of the muscular dystrophy gene myotilin does not perturb muscle structure or function in mice. Mol Cell Biol 27, 244–252.

    PubMed  CAS  Google Scholar 

  146. Garvey, S. M., Miller, S. E., Claflin, D. R., Faulkner, J. A. and Hauser, M. A. (2006) Transgenic mice expressing the myotilin T57I mutation unite the pathology associated with LGMD1A and MFM. Hum Mol Genet 15, 2348–2362.

    PubMed  CAS  Google Scholar 

  147. Sher, R. B., Aoyama, C., Huebsch, K. A., Ji, S., Kerner, J., Yang, Y., et al. (2006) A rostrocaudal muscular dystrophy caused by a defect in choline kinase beta, the first enzyme in phosphatidylcholine biosynthesis. J Biol Chem 281, 4938–4948.

    PubMed  CAS  Google Scholar 

  148. Buj-Bello, A., Laugel, V., Messaddeq, N., Zahreddine, H., Laporte, J., Pellissier, J. F., et al. (2002) The lipid phosphatase myotubularin is essential for skeletal muscle maintenance but not for myogenesis in mice. Proc Natl Acad Sci U S A 99, 15060–15065.

    PubMed  CAS  Google Scholar 

  149. Sullivan, T., Escalante-Alcalde, D., Bhatt, H., Anver, M., Bhat, N., Nagashima, K., et al. (1999) Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J Cell Biol 147, 913–920.

    PubMed  CAS  Google Scholar 

  150. Arimura, T., Helbling-Leclerc, A., Massart, C., Varnous, S., Niel, F., Lacene, E., et al. (2005) Mouse model carrying H222P-Lmna mutation develops muscular dystrophy and dilated cardiomyopathy similar to human striated muscle laminopathies. Hum Mol Genet 14, 155–169.

    PubMed  CAS  Google Scholar 

  151. Diaz, F., Thomas, C. K., Garcia, S., Hernandez, D. and Moraes, C. T. (2005) Mice lacking COX10 in skeletal muscle recapitulate the phenotype of progressive mitochondrial myopathies associated with cytochrome c oxidase deficiency. Hum Mol Genet 14, 2737–2748.

    PubMed  CAS  Google Scholar 

  152. Mankodi, A., Logigian, E., Callahan, L., McClain, C., White, R., Henderson, D., et al. (2000) Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat. Science 289, 1769–1773.

    PubMed  CAS  Google Scholar 

  153. Seznec, H., Agbulut, O., Sergeant, N., Savouret, C., Ghestem, A., Tabti, N., et al. (2001) Mice transgenic for the human myotonic dystrophy region with expanded CTG repeats display muscular and brain abnormalities. Hum Mol Genet 10, 2717–2726.

    PubMed  CAS  Google Scholar 

  154. Orengo, J. P., Chambon, P., Metzger, D., Mosier, D. R., Snipes, G. J. and Cooper, T. A. (2008) Expanded CTG repeats within the DMPK 3’ UTR causes severe skeletal muscle wasting in an inducible mouse model for myotonic dystrophy. Proc Natl Acad Sci U S A 105, 2646–2651.

    PubMed  CAS  Google Scholar 

  155. Reddy, S., Smith, D. B., Rich, M. M., Leferovich, J. M., Reilly, P., Davis, B. M., et al. (1996) Mice lacking the myotonic dystrophy protein kinase develop a late onset progressive myopathy. Nat Genet 13, 325–335.

    PubMed  CAS  Google Scholar 

  156. Kanadia, R. N., Johnstone, K. A., Mankodi, A., Lungu, C., Thornton, C. A., Esson, D., et al. (2003) A muscleblind knockout model for myotonic dystrophy. Science 302, 1978–1980.

    PubMed  CAS  Google Scholar 

  157. Malicdan, M. C., Noguchi, S., Nonaka, I., Hayashi, Y. K. and Nishino, I. (2007) A Gne knockout mouse expressing human GNE D176V mutation develops features similar to distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy. Hum Mol Genet 16, 2669–2682.

    PubMed  CAS  Google Scholar 

  158. Tronche, F., Kellendonk, C., Kretz, O., Gass, P., Anlag, K., Orban, P. C., et al. (1999) Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat Genet 23, 99–103.

    PubMed  CAS  Google Scholar 

  159. Yang, X., Arber, S., William, C., Li, L., Tanabe, Y., Jessell, T. M., et al. (2001) Patterning of muscle acetylcholine receptor gene expression in the absence of motor innervation. Neuron 30, 399–410.

    PubMed  CAS  Google Scholar 

  160. Arber, S., Han, B., Mendelsohn, M., Smith, M., Jessell, T. M. and Sockanathan, S. (1999) Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity. Neuron 23, 659–674.

    PubMed  CAS  Google Scholar 

  161. Schwander, M., Leu, M., Stumm, M., Dorchies, O. M., Ruegg, U. T., Schittny, J., et al. (2003) Beta1 integrins regulate myoblast fusion and sarcomere assembly. Dev Cell 4, 673–685.

    PubMed  CAS  Google Scholar 

  162. Bruning, J. C., Michael, M. D., Winnay, J. N., Hayashi, T., Horsch, D., Accili, D., et al. (1998) A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell 2, 559–569.

    PubMed  CAS  Google Scholar 

  163. Tallquist, M. D., Weismann, K. E., Hellstrom, M. and Soriano, P. (2000) Early myotome specification regulates PDGFA expression and axial skeleton development. Development 127, 5059–5070.

    PubMed  CAS  Google Scholar 

  164. Feltri, M. L., D’Antonio, M., Previtali, S., Fasolini, M., Messing, A. and Wrabetz, L. (1999) P0-Cre transgenic mice for inactivation of adhesion molecules in Schwann cells. Ann N Y Acad Sci 883, 116–123.

    PubMed  CAS  Google Scholar 

  165. Young, P., Qiu, L., Wang, D., Zhao, S., Gross, J. and Feng, G. (2008) Single-neuron labeling with inducible Cre-mediated knockout in transgenic mice. Nat Neurosci 11, 721–728.

    PubMed  CAS  Google Scholar 

  166. Feng, G., Mellor, R. H., Bernstein, M., Keller-Peck, C., Nguyen, Q. T., Wallace, M., et al. (2000) Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28, 41–51.

    PubMed  CAS  Google Scholar 

  167. Misgeld, T., Kerschensteiner, M., Bareyre, F. M., Burgess, R. W. and Lichtman, J. W. (2007) Imaging axonal transport of mitochondria in vivo. Nat Methods 4, 559–561.

    Google Scholar 

  168. Zuo, Y., Lubischer, J. L., Kang, H., Tian, L., Mikesh, M., Marks, A., et al. (2004) Fluorescent proteins expressed in mouse transgenic lines mark subsets of glia, neurons, macrophages, and dendritic cells for vital examination. J Neurosci 24, 10999–11009.

    PubMed  CAS  Google Scholar 

  169. Wichterle, H., Lieberam, I., Porter, J. A. and Jessell, T. M. (2002) Directed differentiation of embryonic stem cells into motor neurons. Cell 110, 385–397.

    PubMed  CAS  Google Scholar 

  170. Livet, J., Weissman, T. A., Kang, H., Draft, R. W., Lu, J., Bennis, R. A., et al. (2007) Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. Nature 450, 56–62.

    PubMed  CAS  Google Scholar 

  171. Coleman, M. P., Conforti, L., Buckmaster, E. A., Tarlton, A., Ewing, R. M., Brown, M. C., et al. (1998) An 85-kb tandem triplication in the slow Wallerian degeneration (Wlds) mouse. Proc Natl Acad Sci U S A 95, 9985–9990.

    PubMed  CAS  Google Scholar 

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  1. The Jackson Laboratory, Bar Harbor, ME, USA

    Robert W. Burgess, Gregory A. Cox & Kevin L. Seburn

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  1. Robert W. Burgess
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  1. The Jackson Laboratory, Main Street 600, Bar Harbor, 04609, Maine, USA

    Gabriele Proetzel

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    Michael V. Wiles

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Burgess, R.W., Cox, G.A., Seburn, K.L. (2010). Neuromuscular Disease Models and Analysis. In: Proetzel, G., Wiles, M. (eds) Mouse Models for Drug Discovery. Methods in Molecular Biology, vol 602. Humana Press. https://doi.org/10.1007/978-1-60761-058-8_20

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