Motor neurone disease and animal models

Neurobiology of Disease

Volumn 1, Issue 1-2, 1994, Pages 3-11

  Price, Donald L ^a,b   Cleveland, Don W ^a   Koliatsos, Vassilis E ^a  

^a JOHNS HOPKINS UNIVERSITY   (United States)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Amyotrophic lateral sclerosis; Neurofribrillary pathology; Neurotrophins; SOD1 mutations; Sodium pentosan polysulphate

Indexed keywords

ANIMAL; DISEASE MODEL; DOG; MOTOR NEURON DISEASE; MOUSE; NERVE DEGENERATION; PATHOPHYSIOLOGY; RAT; REVIEW;

ANIMALS; DISEASE MODELS, ANIMAL; DOGS; MICE; MOTOR NEURON DISEASE; NERVE DEGENERATION; RATS;

EID: 0028535671     PISSN: 09699961     EISSN: None     Source Type: Journal    
DOI: 10.1006/nbdi.1994.0002     Document Type: Review

References (118)

1. Appel S.H. (1993) Excitotoxic neuronal cell death in amyotrophic lateral sclerosis. Trends Neurosci. 16, 3-5.
2. Avraham K.B., Schickler M., Sapoznikov D., Yarom R. & Groner Y. (1988) Down’s syndrome; abnormal neuromuscular junction in tongue of transgenic mice with elevated levels of human Cu/Zn-superoxide dismutase. Cell 54, 823-829.
3. Avraham K.B., Sugarman H., Rotshenker S. & Groner Y. (1991) Down’s syndrome morphological remodelling and increased complexity in the neuromuscular junction of transgenic CuZn-superoxide dismutase mice. J. Neurocytol 20, 208-215.
4. Banker B.Q. (1986) The pathology of motor neurone disorders. In: Myology. Vol. II. A.G. Engel & B.Q. Banker (eds), pp. 2031-2067. McGraw Hill, New York.
5. Beckman J.S., Carson M., Smith C.D. & Koppenol W.H. (1993) ALS, SOD and peroxynitrite. Nature 364, 584.
6. Bergeron C., Beric-Maskarel K., Muntasser S., Weyer L., Somerville MJ. & Percy M.E. (1994) Neurofilament light and polyadenylated mRNA levels are decreased in amyotrophic lateral sclerosis motor neurons. J. Neuropathol. Exp. Neurol. 53, 221-230.
7. Bodian D. & Mellors R.C. (1945) The regenerative cycle of motoneurones, with special reference to phosphatase activity J. Exp. Med. 81, 469-488.
8. Borchelt D.R., Lee M.K., Slunt H.H., Guarmeri M., Xu Z.-S., Wong PC., Brown R.H., Jr Price D.L., Sisodia S.S. & Cleveland D.W. (1994) Superoxide dismutase 1 with mutations linked to familial amyotrophic lateral sclerosis possess significant activity. Proc. Natl.Acad. Sci USA 91, 8292-8296.
9. Brady S.T. (1993) Motor neurons and neurofilaments in sickness and in health. Cell 73, 1-3.
10. 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 lipofuscinosis (Batten’s disease). Ann Neurol. 33, 381-385.
11. Brownell B., Oppenheimer D.R. & Hughes J.T. (1970) The central nervous system in motor neurone disease. J. Neurol. Neurosurg. Psychiatry 33, 338-357.
12. Callahan L. M., Wylen E. L., Messer A. & Mazurkiewicz J. E. (1991) Neurofilament distribution is altered in the Mnd (motor neuron degeneration) mouse.J. Neuropathol. Exp. Neurol. 50, 491-504.
13. Carroll P.T., Price D.L., Griffin J.W. & Morris J. (1978) Tetanus toxin: immunocytochemical evidence for retrograde transport. Neurosci. Lett. 8, 335-339.
14. Caskey C.T., Pizzuti A., Fu, Y-H., Fenwick R. G. Jr. & Nelson D. L. (1992) Triplet repeat mutations in human disease. Science 256, 784-789.
15. Chou S.M. (1992) Pathology-light microscopy of amyotrophic lateral sclerosis. In: Handbook of Amyotrophic Lateral Sclerosis, Neurological Disease and Therapy, Vol. 12. R.A. Smith (ed.), pp. 133-181. Marcel Dekker, NewYork.
16. Clark A.W., Griffin J. W. & Price D. L. (1980) The axonal pathology in chronic IDPN intoxication. J Neuropathol. Exp. Neurol. 39, 42-55.
17. Clark A.W, Parhad I.M., Griffin J.W, & Price D.L. (1984) Neurofilamentous axonal swellings as a normal finding in the spinal anterior horn of man and other primates. J. Neuropathol. Exp. Neurol 43, 253-262.
18. Clatterbuck R.E., Price D.L. & Koliatsos VE. (1994) Further characterization of the effects of brain-derived neurotrophic factor and ciliary neurotrophic factor on axotomized neonatal and adult mammalian motor neurons. J Comp. Neurol. 342, 45-56.
19. Cork L.C., Griffin J.W, Munnell J.F, Lorenz M.D., Adams RJ. & Price D.L. (1979) Hereditary canine spinal muscular atrophy. J Neuropathol Exp Neurol 38, 209-221.
20. Cork L.C., Griffin J.W., Choy C., Padula C.A. & Price D.L. (1982) Pathology of motor neurons in accelerated Hereditary Canine Spinal Muscular Atrophy Lab Invest. 46, 89-99.
21. Cork L.C., Altschuler RJ., Bruha PJ., Morris J.M., Lloyd D.G., Loats H.L., Griffin J.W. & Price D.L. (1989a) Changes in neuronal size and neurotransmitter marker in Hereditary Canine Spinal Muscular Atrophy. Lab. Invest. 61, 69-76.
22. Cork L.C., Struble R.G., Gold B.G., DiCarlo C., Fahnestock K.E., Griffin J.W. & Price D.L. (1989b) Changes in size of motor axons in Hereditary Canine Spinal Muscular Atrophy. Lab. Invest. 61, 333-342.
23. Cork L.C. (1991) Hereditary Canine Spinal Muscular Atrophy: an animal model of motor neuron disease. Can.J. Neurol. Sci. 18, 432-434.
24. Côté F., Collard J.-F & Julien J.-P (1993) Progressive neurono-pathy in transgenic mice expressing the human neurofilament heavy gene: a mouse model of amyotrophic lateral sclerosis. Cell 73, 35-46.
25. Davies A.M. (1994) Tracking neurotrophin function. Nature 368, 193-194.
26. Delisle M.B. & Carpenter S. (1984) Neurofibrillary axonal swellings and amyotrophic lateral sclerosis.J. Neurol. Sci. 63, 241-250.
27. Deng H.-X., Hentati A., Tainer J.A. et al. (1993) Amyotrophic lateral sclerosis and structural defects in Cu, Zn superoxide dismutase. Science 261, 1047-1051.
28. Doyu M., Sobue G., Mukai E., Kachi T., Yasuda T., Mitsuma T. & Takahashi A. (1992) Severity of X-linked recessive bulbospinal neuronopathy correlates with size of the tandem CAG repeat in androgen receptor gene. Ann. Neurol. 32, 707-710.
29. Eyer J. & Peterson A. (1994) Neurofilament-deficient axons and perikaryal aggregates in viable transgenic mice expressing a neurofilament-& bgr;-galactosidase fusion protein. Neuron 12, 389-405.
30. Fischbeck K.H., Souders D. & La Spada A. (1991) A candidate gene for X-linked spinal muscular atrophy. In: Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases, Advances in Neurology, Vol. 56. L.P. Rowland (ed.), pp. 209-213. Raven Press, New York.
31. Fridovich I. (1986) Superoxide dismutases. Adv. Enzymol. Relat. Areas Mol. Biol. 58, 61-97.
32. Gold B.G., Griffin J.W., Price D L., Cork L.C. & Lowndes H.E. (1986) Structural correlates of physiological abnormalities in p, p'-iminodipropionitrile. Brain Res. 362, 205-213.
33. Griffin J.W., Drachman D.B. & Price D.L. (1976) Fast axonal transport in motor nerve regeneration. J Neurobiol. 7, 355-370.
34. Griffin J.W., Price D.L., Engel W.K. & Drachman D.B. (1977) The pathogenesis of reactive axonal swellings role of axonal transport.J. Neuropathol. Exp. Neurol. 36, 214-227.
35. Griffin J.W., Hoffman P.N., Clark A.W., Carroll P.T. & Price D.L. (1978) Slow axonal transport of neurofilament proteins: impairment by p, p'-iminodipropionitrile administration. Science 202, 633-635.
36. Griffin J.W., Price D.L., Drachman D.B. & Morris J. (1981) Incorporation of axonally transported glycoproteins into axolemma during nerve regeneration. J. Cell Biol. 88, 205-214.
37. Griffin J.W., Cork L.C., Adams R J. & Price D. L (1982) Axonal transport fin Hereditary Canine Spinal Muscular Atrophy (HCSMA). J. Neuropathol. Exp. Neurol. 41, 370.
38. Griffin J.W., Fahnestock K.E., Price D.L. & Cork L.C. (1983a) Cytoskeletal disorganization induced by local application of p, p'-iminodipropionitrile and 2, 5-hexanedione Ann. Neurol. 14, 55-61.
39. Griffin J.W., Price D.L. & Hoffman PN. (1983b) Neurotoxic probes of the axonal cytoskeleton. Trends Neurosci. 6, 490-495.
40. Gurney M.E., Pu H., Chiu A.Y., Dal Canto M.C., Polchow C.Y., Alexander D.D., Caliendo J., Hentati A., Kwon YW, Deng H.-X., Chen W., Zhai P, Sufit R.L. & Siddique T. (1994) Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science 264, 1772-1775.
41. Halliwell B. (1992) Reactive oxygen species and the central nervous system. In: Free Radicals in the Brain. Aging, Neurological and Mental Disorders. L. Packer, L. Prilipko & Y. Christen (eds), pp. 21-40. Springer-Verlag, Berlin.
42. Hamida M.B. & Hentati F. (1991) Juvenile amyotrophic lateral sclerosis and related syndromes. In: Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases, Advances in Neurology, Vol. 56, L.P. Rowland (ed.), pp. 175-179. Raven Press, New York.
43. Harding A. E. (1993) Inherited neuronal atrophy and degeneration predominantly of lower motor neurones. In: Peripheral Neuropathy, Third edition P J. Dyck, PK. Thomas, J.W. Griffin, PA. Low, & J.F. Poduslo (eds), pp. 1051-1064. W.B. Saunders, Philadelphia.
44. Hausmanowa-Petrusewicz I. (1991) Spinal muscular atrophies: how many types? In: Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases, Advances in Neurology, Vol. 56. L.P. Rowland (ed.), pp 157-167. Raven Press, New York.
45. Hirano A. (1991) Cytopathology of amyotrophic lateral sclerosis. In: Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases, Advances in Neurology, Vol. 56 L.P. Rowland (ed.), pp. 91-101. Raven Press, New York.
46. Hirano A. & Kato S. (1992) Fine structural study of sporadic and familial amyotrophic lateral sclerosis. In: Handbook ofAmyotrophic Lateral Sclerosis, Neurological Disease and Therapy, Vol. 12. R.A. Smith (ed.), pp 183-192. Marcel Dekker, New York.
47. Hoffman P.N., Griffin J.W. & Price D.L. (1984) Control of axonal caliber by neurofilament transport. J. Cell Biol. 99, 705-714.
48. Hoffman P. N., Thompson G.W, Griffin J. W. & Price D. L. (1985) Changes in neurofilament transport coincide temporally with alterations in the caliber of axons in regenerating motor fibers. J. Cell Biol. 101, 1332-1340.
49. Hoffman P.N., Cleveland D.W., Griffin J.W, Landes P.W., Cowan N.J. & Price D.L. (1987) Neurofilament gene expression a major determinant of axonal caliber. Proc. Natl.Acad Sci. USA 84, 3472-3476.
50. Imlay J.A. & Linn S. (1988) DNA damage and oxygen radical toxicity. Science 240, 1302-1309.
51. Jones K.R., Fariñas I., Backus C. & Reichardt L.F (1994) Targeted disruption of the BDNF gene perturbs brain and sensory neurone development but not motor neuron development Cell 76, 989-999.
52. Klein R., Smeyne R.J., Wurst W., Long L.K., Auerbach B.A., Joyner A.L. & Barbacid M. (1993) Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death. Cell 75, 113-122.
53. Koliatsos V.E., Nauta H.J.W., Clatterbuck R.E., Holtzman D.M., Mobley W.C. & Price D.L. (1990) Mouse nerve growth factor prevents degeneration of axotomized basal forebrain cholinergic neurons in the monkey. J. Neurosci. 10, 3801-3813.
54. Koliatsos V.E., Applegate M.D., Knuuml k., sel B., Junard E.O., Burton L.E., Mobley W. C., Hefti F. F. & Price D. L. (1991a) Recombinant human nerve growth factor prevents retrograde degeneration of axotomized basal forebrain cholinergic neurones in the rat Exp. Neurol. 112, 161-173.
55. Koliatsos V.E., Crawford T.O. & Price D.L. (1991b) Axotomy induces nerve growth factor receptor immunoreactivity in spinal motor neurons. Brain Res. 549, 297-304.
56. Koliatsos V. E., Clatterbuck R. E., Winslow J. W, Cayouette M. H. & Price D. L. (1993) Evidence that brain-derived neurotrophic factor is a trophic factor for motor neurons in vivo. Neuron 10, 359-367.
57. Koliatsos V.E., Cayouette M.H., Berkemeier L.R., Clatterbuck R.E., Price D.L. & Rosenthal A. (1994) Neurotrophin 4/5 is a trophic factor for mammalian facial motor neurons. Proc. Natl. Acad. Sci. USA 91, 3304-3308.
58. Koo E.H., Hoffman P.N. & Price D.L. (1988) Levels of neurotransmitter and cytoskeletal mRNAs during nerve regeneration in sympathetic ganglia. Brain Res. 449, 361-363.
59. Koo E.H., Sisodia S.S., Archer D.R., Martin L. J., Weidemann A., Beyreuther K., Fischer P., Masters C. L. & Price D. L. (1990) Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. Proc. Natl.Acad. Sci. USA 87, 1561-1565.
60. Kuncl R.W., Crawford T.O., Rothstein J.D. & Drachman D.B. (1992) Motor neurone diseases. In: Diseases of the Nervous System, Clinical Neurobiology, Second edition, Vol. II. A.K. Asbury, G.M. McKhann, & W.I. McDonald (eds), pp. 1179-1208.'WB. Saunders, Philadelphia.
61. La Spada A.R., Wilson E.M., Lubahn D.B., Harding A.E. & Fischbeck K.H. (1991) Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352, 77-79.
62. Lee M.K., Xu Z., Wong PC. & Cleveland D.W. (1993) Neurofilaments are obligate heteropolymers in vivo. J. Cell Biol 122, 1337-1350.
63. Lee M.K. & Cleveland D.W (1994a) Neurofilament function and dysfunction: involvement in axonal growth and neuronal disease. Curr. Opin. Cell Biol. 6, 34-40.
64. Lee M.K., Marszalek J.R. & Cleveland D.W (1994) Expression of a mutant neurofilament subunit causes massive, selective motor neuron death and ALS-like motor neuron disease. Neuron (in press).
65. Lipton S.A. & Rosenberg PA. (1994) Excitatory amino acids as a final common pathway for neurologic disorders N. Engl. J. Med. 330, 613-622.
66. Lorenz M.D., Cork L.C., Griffin J. W, Adams R. J. & Price D. L. (1979) Hereditary spinal muscular atrophy in Brittany spaniels: clinical manifestations. J Am. Vet. Med.Assoc. 175, 833-839.
67. Lowe J., Mayer R.J. & Landon M. (1993) Ubiquitin in neurodegenerative diseases. Brain Pathol. 3, 55-65.
68. Manetto V., Sternberger N.H., Perry G., Sternberger L.A. & Gambetti P. (1988) Phosphorylation ofneurofilaments is altered in amyotrophic lateral sclerosis.J. Neuropathol. Exp Neurol. 47, 642-653.
69. 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.
70. Matsuura T., Demura T., Aimoto Y, Mizuno T., Moriwaka F & Tashiro K. (1992) Androgen receptor abnormality in X-linked spinal and bulbar muscular atrophy. Neurology 42, 1724-1726.
71. Mazurkiewicz J.E. (1991) Ubiquitin deposits are present in spinal motor neurones in all stages of the disease in the motor neuron degeneration Mnd mutant of the mouse. Neurosci Lett. 128, 182-186.
72. McNamara J.O. & Fridovich I. (1993) Did radicals strike Lou Gehrig? Nature 362, 20-21.
73. Melki J., Abdelhak S., Sheth P et al. (1990) Gene for chronic proximal spinal muscular atrophies maps to chromosome 5q. Nature 344, 767-768.
74. Melki J., Lefebvre S., Burglen L., Burlet P, Clermont O., Millasseau P, Reboullet S., Benichou B., Zeviani M., Le Paslier D., Cohen D., Weissenbach J. & Munnich A. (1994) De novo and inherited deletions of the 5q13 region in spinal muscular atrophies. Science 264, 1474-1477.
75. Messer A. & Flaherty L. (1986) Autosomal dominance in a late-onset motor neuron disease in the mouse.J. Neurogenet. 3, 345-355.
76. Messer A., Strominger N.L. & Mazurkiewicz J.E. (1987) Histo-pathology of the late-onset motor neuron degeneration Mnd mutant in the mouse. J. Neurogenet. 4, 201-213.
77. Messer, A. (1992a) Animal models of amyotrophic lateral sclerosis In: Handbook of Amyotrophic Lateral Sclerosis, Neurological Disease and Therapy, Vol. 12. R.A. Smith (ed.), pp. 433-451. Marcel Dekker, New York.
78. Messer A., Plummer J., Maskin P, Coffin J.M. & Frankel WN. (1992b) Mapping of the motor neuron degeneration Mnd gene, a mouse model of amyotrophic lateral sclerosis (ALS). Genomics 18, 797-802.
79. Messer A. & Plummer J. (1993) Accumulating autofluorescent material as a marker for early changes in the spinal cord of the Mnd mouse. Neuromusc. Disord. 3, 129-134.
80. Monaghan D.T., Bridges RJ. & Cotman C.W. (1989) The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system. Annu. Rev. Pharmacol. Toxicol. 29, 365-402.
81. Monteiro MJ., Hoffman P.N., Gearhart J.D. & Cleveland D.W (1990) Expression of NF-L in both neuronal and nonneuronal cells of transgenic mice: increased neurofilament density in axons without affecting caliber.J. Cell Biol. 111, 1543-1557.
82. Muma N.A., Hoffman P.N., Slunt H.H., Applegate M.D., Lieberburg I. & Price D.L. (1990) Alterations in levels of mRNA coding for neurofilament protein subunits during regeneration Exp. Neurol. 107, 230-235.
83. Munoz D.G., Greene C., Perl D.P. & Selkoe DJ. (1988) Accumulation of phosphorylated neurofilaments in anterior horn motoneurones of amyotrophic lateral sclerosis patients. J. Neuropathol. Exp. Neurol. 47, 9-18.
84. Nissl F (1892) Über die veranderungen der ganglienzellen am facialiskern des kanincheng anch ausreissung der nerven. Allg. Z. Psychiatr. 48, 197-198.
85. Oppenheim R.W, Qin-Wei Y, Prevette D. & Yan Q. (1992) Brain-derived neurotrophic factor rescues developing avian motoneurones from cell death. Nature 360, 755-757.
86. Oppenheimer D.R. & Esin M.M. (1992) Diseases of the basal ganglia, cerebellum and motor neurons. In: Greenfield’s Neuropathology, Fifth edition. J.H. Adams & L.W Duchen (eds), pp 988-1045. Oxford University Press, New York.
87. Palmer D.N., Fearnley I.M., Walker J.E., Hall N.A, Lake B.D., Wolfe L.S., Haltia M., Martinus R.D, & Jolly R.D. (1992) Mitochondrial ATP synthase subunit c storage in the ceroid-lipofuscinoses (Batten disease) Am.J. Med. Genet. 12, 561-567.
88. Pardo C.A., Rabin B.A., Palmer D.N. & Price D.L. (1994) Accumulation ofthe adenosine triphosphate synthase subunit c in the mind mutant mice. A mode for neuronal ceroid lipofuscinosis. Am.J. Pathol. 144, 1-7.
89. Price D.L. & Porter K.R. (1972) The response of ventral horn neurons to axonal transection. J. Cell Biol 53, 24-37.
90. Price D.L. & Griffin J.W. (1977) Tetanus toxin, retrograde axonal transport of systematically administered toxin. Neurosci. Lett. 4, 61-65.
91. Price D.L., Griffin J.W., Hoffman P.N., Cork L.C. & Spencer P.S. (1984) The response of motor neurons to injury and disease. In: Peripheral Neuropathy, Vol. I. PJ. Dyck, P.K. Thomas, E.H. Lambert, & R. Bunge (eds), pp. 732-759. W.B. Saunders, Philadelphia.
92. Price D.L., Borchelt D.R., Walker L.C. & Sisodia S.S. (1992a) Toxicity of synthetic Aß peptides and modeling of Alzheimer’s disease. Neurobiol.Aging 13, 623-625.
93. Price D.L., Martin L.J., Clatterbuck R.E., Koliatsos V.E., Sisodia S.S., Walker L.C. & Cork L.C. (1992b) Neuronal degeneration in human diseases and animal models J Neurobiol. 23, 1277-1294.
94. Rosen D.R., Siddique T., Patterson D. et al. (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362, 59-62.
95. Rosenfeld J., Dorman M.E., Griffin J.W., Gold B.G., Sternberger L.A., Sternberger N.H. & Price D.L. (1987) Distribution of neurofilament antigens after axonal injury. J. Neuropathol. Exp. Neurol. 46, 269-282.
96. Rothstein J.D., Martin LJ. & Kuncl R.W. (1992) Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N Engl.J. Med. 326, 1464-1468.
97. Rothstein J.D., Jin L., Dykes-Hoberg M. & Kuncl R.W. (1993) Chronic inhibition of glutamate uptake produces a model of slow neurotoxicity Proc. Natl.Acad. Sci. USA 90, 6591-6595.
98. Rothstein J.D., Bristol L.A., Hosler B., Brown R.H.Jr. & Kuncl R.W. (1994) Chronic inhibition of superoxide dismutase produces apoptotic death of spinal neurons. Proc. Natl. Acad. Sci. USA 91, 4155-4159.
99. Sack G. H., Jr., Cork L. C., Morris J.M., Griffin J.W & Price D.L. (1984) Autosomal dominant inheritance of Hereditary Canine Spinal Muscular Atrophy. Ann. Neurol. 15, 369-373.
100. Sasaki S., Kamei H., Yamane K. & Maruyama S. (1988) Swelling of neuronal processes in motor neuron disease. Neurology 38, 1114-1118.
101. Schmalbruch H., Jensen H.-J. S., Bj Aeligrg M., Kamieniecka Z. & Kurland L. (1991) A new mouse mutant with progressive motor neuronopathy. J. Neuropathol. Exp. Neurol. 50, 192-204.
102. Sendtner M., Kreutzberg G.W. & Thoenen H. (1990) Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy. Nature 345, 440-441.
103. Sendtner M., Holtmann B., Kolbeck R., Thoenen H. & Barde Y-A. (1992a) Brain-derived neurotrophic factor prevents the death of motoneurones in newborn rats after nerve section. Nature 360, 757-759.
104. Sendtner M., Schmalbruch H., Stöckli K.A., Carroll P., Kreutzberg G.W. & Thoenen H. (1992b) Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy. Nature 358, 502-504.
105. Sendtner M., St oumlockll K.A., Carroll P, Kreutzberg G.W, Thoenen H. & Schmalbruch H. (1992c) More on motor neurons. Nature 360, 541-542.
106. Siddique T., Pencak-Vance M.A., Brooks B.R., Roos R.P, Hung W-Y, Antel J.P, Munsat T.L., Phillips K., Warner K., Speer M., Bias WB., Siddique N.A. & Roses A.D. (1989) Linkage analysis in familial amyotrophic lateral sclerosis. Neurology 39, 919-925.
107. 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. et al. (1991) Linkage of a gene causing familial amyotrophic lateral sclerosis to chromosome 21 and evidence of genetic-locus heterogeneity. N. Engl.J. Med. 324, 1381-1384.
108. Smith R.A. (1992) In. Handbook of Amyotrophic Lateral Sclerosis, Neurological Disease and Therapy, Vol. 12. Marcel Dekker, New York.
109. Snider W.D., Eliott J.L. & Yan Q. (1992) Axotomy-induced neuronal death during development. J. Neurobiol. 23, 123l-1246.
110. Snider W.D. (1994) Functions ofthe neurotrophins during nervous system development: what the knockouts are teaching us. Cell 77, 627-638.
111. Stadtman E.R. (1992) Protein oxidation and aging. Science 257, 1220-1224.
112. Tandan R. & Bradley WG. (1985) Amyotrophic lateral sclerosis Part 1. Clinical features, pathology, and ethical issues in management Ann. Neurol. 18, 271-280.
113. Troy C.M., Muma N.A., Greene L.A., Price D.L. & Shelanski M.L. (1990) Regulation ofperipherin and neurofilament expression in regenerating rat motor neurons Brain Res. 529, 232-238.
114. Tsai G., Stauch-Slusher B., Sim L., Hedreen J.C., Rothstein J.D., Kuncl R. & Coyle J.T. (1991) Reductions in acidic amino acids and N-acetylaspartylglutamate in amyotrophic lateral sclerosis CNS. Brain Res. 556, 151-156.
115. Vrbova G., Greensmith L. & Sieradzan K. (1992) Motor neuron disease model. Nature 360, 216.
116. Williams D.B. & Windebank AJ. (1993) Motor neuron disease. In: Peripheral Neuropathy, Third edition. RJ. Dyck, PK. Thomas, J.W. Griffin, R.A. Low & J.F. Roduslo (eds), pp. 1028-1050. W B. Saunders, Philadelphia.
117. Xu Z., Cork L.C., Griffin J.W. & Cleveland D.W. (1993) Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease. Cell 73, 23-33.
118. Yan Q., Elliott J. & Snider W.D. (1992) Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. Nature 360, 753-755.