Intramuscular grafts of myoblasts genetically modified to secrete glial cell line-derived neurotrophic factor prevent motoneuron loss and disease progression in a mouse model of familial amyotrophic lateral sclerosis

Human Gene Therapy

Volumn 10, Issue 11, 1999, Pages 1853-1866

  Mohajeri, M Hasan ^a,b   Figlewicz, Denise A ^c   Bohn, Martha C ^a,d  

^a NORTHWESTERN UNIVERSITY   (United States)

^b UNIVERSITY HOSPITAL OF PSYCHIATRY   (Switzerland)

^c UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

^d Children's Mem Inst Educ and Res   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA GALACTOSIDASE; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; VIRUS VECTOR;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL SIZE; CONTROLLED STUDY; DISEASE COURSE; ESCHERICHIA COLI; GENE MUTATION; GENE THERAPY; GENETIC ENGINEERING; GENETIC TRANSFECTION; HORMONE RELEASE; MOTOR PERFORMANCE; MOUSE; MUSCLE ATROPHY; MYOBLAST; NERVE DEGENERATION; NONHUMAN; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SPINAL CORD MOTONEURON; TISSUE DISTRIBUTION; TISSUE GRAFT; TRANSGENIC MOUSE;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; BETA-GALACTOSIDASE; CELL TRANSPLANTATION; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; GENE THERAPY; GENETIC VECTORS; GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR; HUMANS; MICE; MOTOR NEURONS; MUSCLE, SKELETAL; NERVE GROWTH FACTORS; NERVE TISSUE PROTEINS; RETROVIRIDAE; TRANSDUCTION, GENETIC;

ANIMALIA; ESCHERICHIA COLI; MUS MUSCULUS; PHOENIX;

EID: 0033587480     PISSN: 10430342     EISSN: None     Source Type: Journal    
DOI: 10.1089/10430349950017536     Document Type: Article

References (86)

1. ABERCROMBIE, M. (1946). Estimation of nuclear population from microtome sections. Anat. Rec. 94, 239-247.
2. BARR, E., and LEIDEN, J.M. (1991). Systemic delivery of recombinant proteins by genetically modified myoblasts. Science 254, 1507-1509.
3. BAUMGARTNER, B.J., and SHINE, H.D. (1997). Targeted transduction of CNS neurons with adenoviral vectors carrying neurotrophic factor genes confers neuroprotection that exceeds the transduced population. J Neurosci. 17, 6504-6511.
4. BAUMGARTNER, B.J., and SHINE, H.D. (1998). Neuroprotection of spinal motoneurons following targeted transduction with an adenoviral vector carrying the gene for glial cell line-derived neurotrophic factor. Exp. Neurol. 153, 102-112.
5. BLAU, H.M., and WEBSTER, C. (1981). Isolation and characterization of human muscle cells. Proc. Natl. Acad. Sci. U.S.A. 78, 5623-5627.
6. BLAU, H.M., DHWAN, J., and PAVLATH, G.K. (1993). Myoblasts in pattern formation and gene therapy. Trends Genet. 9, 269-274.
7. BURAZIN, T.C.D., and GUNDLACH, A.L. (1998). Up-regulation of GDNFR-a and c-ret mRNA in facial motor neurons following facial nerve injury in the rat. Brain Res. Mol. Brain Res. 55, 331-336.
8. BURNS, J.C., FRIEDMAN, T., DRIEVER, W. BURRASCANO, M., and YEE, J.K. (1993). Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: Concentration to a very high titer and efficient gene transfer into mammalian and nonmammalian cells. Proc. Natl. Acad. Sci. U.S.A. 90, 8033-8037.
9. CHIU, A.Y., ZHAI, P., DALCANTO, M.C., PETERS, T.M., KWON, Y.W., PRATTIS, S.M., and GURNEY, M.E. (1995). Age-dependent penetrance of disease in a transgenic mouse model of familial amyotrophic lateral sclerosis. Mol. Cell. Neurosci. 6, 349-362.
10. CHOI-LUNDBERG, D.L., and BOHN, M.C. (1995). Ontogeny and distribution of glial cell line-derived neurotrophic factor (GDNF) mRNA in rat. Dev. Brain Res. 85, 80-88.
11. CHOI-LUNDBERG, D.L., LIN, Q., CHANG, Y.-N., CHIANG, Y.L., HAY, C.M., MOHAJERI, H., DAVIDSON, B.L., and BOHN, M.C. (1997). Dopaminergic neurons protected from degeneration by GDNF gene therapy. Science 275, 838-841.
12. CHOI-LUNDBERG, D.L., LIN, Q., SCHALLERT, T., CRIPPENS, D., DAVIDSON, B.L., CHANG, Y.-N., CHIANG, Y.L., QIAN, J., BARDWAJ, L., and BOHN, M.C. (1998). Behavioral and cellular protection of rat dopaminergic neurons elicited by an adenoviral vector encoding glial cell line-derived neurotrophic factor. Exp. Neurol. 154, 261-275.
13. COLLARD, J.-F., COTE, F., and JULIEN, J.-P. (1995). Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis. Nature (London) 375, 61-64.
14. COUGHENOUR, L., McCLEAN, J.R., and PARKER, R.B. (1977). A new device for rapid measurement of impaired motor functions in mice. Pharmacol. Biochem. Behav. 6, 6460-6464.
15. DAL CANTO, M.C., and GURNEY, M.E. (1994). The development of central nervous system pathology in a murine transgenic model of human amyotrophic lateral sclerosis. Am. J. Pathol. 145, 1171-1279.
16. DANOS, O., and MULLIGAN, R.C. (1988). Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges. Proc. Natl. Acad. Sci. U.S.A. 85, 6460-6464.
17. DENG, H.X., HENTATI, A., RAINER, J.A., IQBAL, Z., CAYABYAB, Z., HUNG, W.-Y., GETZOFF, E.D., HU, P., HERZFELDT, B., ROOS, R.P., WARNER, C., DENG, G., SORIANO, E., SMYTH, C., PARGE, H.E., AHMED, A., ROSES, A.D., HALLEWELL, R.A., PERICAK-VANCE, M.A., and SIDDIQUE, T. (1993). Amyotrophic lateral sclerosis and structural defects in Cu,Zn superoxide dismutase. Science 261, 1047-1051.
18. DHAWAN, J., PAN, L.C., PAVLATH, G.K., TRAVIS, A.T., LANCTOT, A.M., and BLAU, H.M. (1991). Systemic delivery of human growth hormone by injection of genetically engineered myoblasts. Science 254, 1509-1512.
19. FUNAKOSHI, H., BELLUARDO, N., ARENAS, E., YAMAMOTO, Y., CASABONA, A., PERSSON, H., and IBANEZ, C.F. (1995). Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons. Science 268, 1495-1499.
20. GASIOR, M., CARTER, R.B., GOLDBERG, S.R., and WITKIN, J.M. (1997). Anticonvulsant and behavioral effects of neuroactive steroids alone and in conjunction with diazepam. J. Pharmacol. Exp. Ther. 282, 543-553.
21. GIBSON, U., HEID, C., and WILLIAMS, P. (1996). A novel method for real time quantitative RT-PCR. Genome Res. 6, 995-1001.
22. GLAZNER, G.W., MU, X., and SPRINGER, J.E. (1998). Localization of glial cell line-derived neurotrophic factor receptor alpha and c-ret mRNA in rat central nervous system. J. Comp. Neurol. 391, 42-49.
23. GRIGNANI, F., KINSELLA, T., MENCARELLI, A., VALTIERI, M., RIGANELLI, D., GRIGNANI, F., LANFRANCONE, L., PESCHLE, C., NOLAN, G.P., and PELICCI, P.G. (1998). High-efficiency gene transfer and selection of hematopoietic progenitor cells with a hybrid EBV/retroviral vector expressing the green fluorescent protein. Cancer Res. 58, 14-19.
24. GURNEY, M.E., PU, H., CHIU, A.Y., DAL CANTO, M.C., POLCHOW, C.Y., ALEXANDER, D.D., CALIENDO, J., HENTATI, A., KWON, Y.W., DENG, H.-X., CHEN, W., ZHAI, P., SUFIT, R.L., and SIDDIQUE, T. (1994). Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 264, 1772-1775.
25. GURNEY, M.E., CUTTING, F.B., ZHAI, P., DOBLE, A., TAYLOR, C.P., ANDRUS, P.R., and HALL, E.D. (1996). Benefit of vitamin E, riluzole and gabapentin in a transgenic mouse model of familial amyotrophic lateral sclerosis. Ann. Neurol. 39, 147-157.
26. HAASE, G., KENNEL, P., PETTMAN, B., VIGNE, E., AKLI, S., REVAH, F., SCHMALBRUCH, H., and KAHN, A. (1997). Gene therapy of murine motor neuron disease using adenoviral vectors for neurotrophic factors. Nature Med 3, 429-436.
27. HEID, C., STEVENS, J., and LIVAK, K.P.W. (1996). Real time quantitative PCR. Genome Res. 6, 986-994.
28. HENDERSON, C. (1995). Neurotrophic factors as therapeutic agents in ALS. Adv. Neurol. 68, 235-240.
29. HENDERSON, C.E., CAMU, W., METTLING, C., GOUIN, A., POULSEN, K., KARIHALOO, M., RULLAMAS, J., EVANS, T., McMAHON, S.B., ARMANINI, M.P., BERKEMEIER, L., PHILLIPS, H.S., and ROSENTHAL, A. (1993). Neurotrophins promote motor neuron survival and are present in embryonic limb bud. Nature (London) 363, 266-270.
30. HENDERSON, C.E., PHILLIPS, H.S., POLLOCK, R.A., DAVIES, A.M., LEMEULLE, C., ARMANINI, M., SIMMON, L., MOFFET, B., VANDLEN, R.A., KOLIATSOS, E., and ROSENTHAL, A. (1994). GDNF: A potent survival factor for motoneurons present in peripheral nerve and muscle. Science 266, 1062-1064.
31. HORELLOU, P., SABATE, O., BUC-CARON, M., and MALLET, J. (1997). Adenovirus-mediated gene transfer to the central nervous system for Parkinson's disease. Exp. Neurol. 144, 131-138.
32. HOTTINGER, A.F., FINE, E.G., GURNEY, M.E., ZURN, A.D., and AEBISCHER, P. (1997). The copper chelator d-penicillamine delays onset of disease and extends survival in a transgenic mouse model of familial amyotrophic lateral sclerosis. Eur. J. Neurosci. 9, 1548-1551.
33. HOUENOU, L., OPPENHEIM, R., LI, L., LO, A., and PREVETTE, D. (1996). Regulation of spinal motoneuron survival by GDNF during development and following injury. Cell Tiss. Res. 286, 219-223.
34. HUARD, J., ACSADI, G., JANI, A., MASSIE, B., and KARPATI, G. (1994). Gene transfer into skeletal muscles by isogenic myoblasts. Hum. Gene Ther. 5, 949-958.
35. INGRAM, D. (1988). Motor performance variability during aging in rodents. Ann. N.Y. Acad. Sci. 515, 70-96.
36. INGRAM, D.K., LONDON, E.D., REYNOLDS, M.A., WALLER, S.B., and GOODRICK, C.L. (1981). Differential effects of age on motor performance in two mouse strains. Neurobiol. Aging 2, 221-227.
37. KAWAMURA, Y., DYCK, P.J., SHIMONO, M., OKAZAKI, H., TATEISHI, J., and DOI, H. (1981). Morphometric comparison of the vulnerability of peripheral motor and sensory neurons in amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol. 40, 667-675.
38. KINOSHITA, I., HUARD, J., and TREMBLAY, J.P. (1994). Utilization of myoblasts from transgenic mice to evaluate the efficacy of myoblast transplantation. Muscle Nerve 17, 975-980.
39. KINOSHITA, I. VILQUIN, J.T., ROY, R., and TREMBLAY, J.P. (1996). Successive injections in mdx mice of myoblasts grown with bFGF. Neuromusc. Disord. 6, 187-193.
40. KINSELLA, T.M., and NOLAN, G.P. (1996). Episomal vectors rapidly and stably produce high-liter recombinant retrovirus. Hum. Gene Ther. 7, 1405-1413.
41. KONG, J., and XU, Z. (1998). Massive mitochondrial degeneration in motor neurons triggers the onset of amyotrophic lateral sclerosis in mice expressing a mutant SOD1. J Neurosci. 18, 3241-3250.
42. KOSTIC, V., GURNEY, M.E., DENG, H.X., SIDDIQUE, T., EPSTEIN, C.J., and PRZEDBORSKI, S. (1997a). Midbrain dopaminergic neuronal degeneration in a transgenic mouse model of familial amyotrophic lateral sclerosis. Ann. Neurol. 41, 497-504.
43. KOSTIC, V., JACKSON-LEWIS, V., DE BILBAO, F., DUBOIS-DAUPHIN, M., and PRZEDBORSKI, S. (1997b). Bcl-2: Prolonging life in a transgenic mouse model of familial amyotrophic lateral sclerosis. Science 277, 559-562.
44. LAU, H.T., YU, M., FONTANA, A., and STOECKERT, C.J. (1996). Prevention of islet allograft rejection with engineered myoblasts expressing FasL in mice. Science 273, 109-112.
45. 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.
46. LEVANON, D., LIEMAN-HURWITZ, J., DAFNI, N., WIGDERSON, M., SHERMAN, L., BERNSTEIN, Y., LAVER-RUDICH, Z., DANCIGER, E., STEIN, O., and GRONER, Y. (1985). Architecture and anatomy of the chromosomal locus in human chromosome 21 encoding the Cu/Zn superoxide dismutase. EMBO J. 4, 7-84.
47. LI, L.X., WU, W.T., LIN, L.F.H., LEI, M., OPPENHEIM, R.W., and HOUENOU, L.J. (1995). Rescue of adult mouse motoneurons from injury-induced cell death by glial cell line-derived neurotrophic factor. Proc. Natl. Acad. Sci. U.S.A. 92, 9771-9775.
48. MANDEL, R.J., SPRATT, S.K., SNYDER, R.O., and LEFF, S.E. (1997). Midbrain injection of recombinant adeno-associated virus encoding rat glial cell line-derived neurotrophic factor protects nigral neurons in a progressive 6-hydroxydopamine-induced degeneration model of Parkinson's disease in rats. Proc. Natl. Acad. Sci. U.S.A. 94, 14083-14088.
49. MATHESON, C.R., WANG, J., COLLINS, F.D., and YAN, Q. (1997). Long-term survival effects of GDNF on neonatal rat facial motoneurons after axotomy. NeuroReport 8, 1739-1742.
50. McHANWELL, S., and BISCOE, T.J. (1981a). The localization of motoneurons supplying the hindlimb muscles of the mouse. Phil. Trans. R. Soc. London B 293, 477-508.
51. McHANWELL, S., and BISCOE, T.J. (1981b). The size of motoneurons supplying hindlimb muscles in the mouse. Proc. R. Soc. London B 213, 201-216.
52. MENDELL, J.R., KISSEL, J.T., AMATO, A.A., KING, W., SIGNORE, L., PRIOR, T.W., SAHENK, Z., BENSON, S., McANDREW, P.E., RICE, E., NAGARAJA, H., STEPHENS, R., LANTRY, L., MARRIS, G.E., and BURGHES, A.H.M. (1995). Myoblast transfer in the treatment of Duchenne's muscular dystrophy. N. Engl. J. Med. 333, 832-838.
53. MENG, Y., LICHTMAN, A.H., BRIDGEN, D.T., and MARTIN, B.R. (1996). Pharmacological potency and biodisposition of phencyclidine via inhalation exposure in mice. Drug Alcohol Dependence 43, 13-22.
54. MILBRANDT, J., DESAUVAGE, F.J.F., BALOH, R.H., LEITNER, M.L., TANSEY, M.G., LAMPE, P.A., HEUCKEROTH, R.O., KOTZBAUER, P.T., SIMBURGER, K.S., GOLDEN, J.P., DAVIES, J.A., VEJSADA, R., KATO, A.C., HYNES, M., SHERMAN, D., NISHIMURA, M., WANG, L.-C., VANDLEN, R., MOFFAT, B., KLEIN, R.D., POULSEN, K., GRAY, C., GARCES, A., HENDERSON, C.E., PHILLIPS, H.S., and JOHNSON, E.M., Jr. (1998). Persephin, a novel neurotrophic factor related to GDNF and neurturin. Neuron 20, 245-253.
55. MILLER, G.W., STALEY, J.K., HEILMAN, C.J., PEREZ, J.T., MASH, D.C., RYE, D.B., and LEVEY, A.I. (1997). Immunochemical analysis of dopamine transporter protein in Parkinson's disease. Ann. Neurol. 41, 530-539.
56. MITSUMOTO, H., KIEDA, K., KLINKOSZ, B., CEDARBAUM, J.M., WONG, V., and LINDSAY, R.M. (1994). Arrest of motor neuron disease in wobbler mice cotreated with CNTF and BDNF. Science 265, 1107-1109.
57. MOHAJERI, M.H., FIGLEWICZ, D.A., and BOHN, M.C. (1998a). Selective loss of alpha motoneurons innervating the medial gastrocnemius muscle in a mouse model of amyotrophic lateral sclerosis. Exp. Neurol. 150, 329-336.
58. MOHAJERI, M.H., CHANG, Y.-N., CHIANG, Y.L., FIGLEWICZ, D.A., and BOHN, M.C. (1998b). Myoblast-mediated ex vivo GDNF gene therapy in a mouse model of amyotrophic lateral sclerosis (ALS). Exp. Neurol. 153, 384.
59. MORGENSTERN, J.P., and LAND, H. (1990). Advanced mammalian gene transfer: High titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line. Nucleic Acids Res. 18, 3587-3596.
60. MORRISON, B.M., GORDON, J.W., RIPPS, M.E., and MORRISON, J.H. (1996). Quantitative immunocytochemical analysis of the spinal cord in G86R superoxide dismutase transgenic mice: Neurochemical correlates of selective vulnerability. J. Comp. Neurol. 30, 619-631.
61. MUDGE, A.W. (1993). Motor neurons find their factors. Nature (London) 363, 213-214.
62. MULDER, D.W., KURLAND, L.T., OFFORD, K.P., and BEARD, C.M. (1986). Familial adult motor neuron disease - amyotrophic lateral sclerosis. Neurology 36, 511-517.
63. MUNSON, J.B., and McMAHON, S.B. (1997). Effects of GDNF on axotomized sensory and motor neurons in adult rats. Eur. J. Neurosci. 9, 1126-1129.
64. NEUMEYER, A.M., DIGREGORIO, D.M., and BROWN, R.H., JR. 1992. Arterial delivery of myoblasts to skeletal muscle. Neurology 42, 2258-2262.
65. NGUYEN, Q.T., PARSADANIAN, A.S., SNIDER, W.D., and LIGHTMAN, J.W. (1998). Hyperinnervation of neuromuscular junctions caused by GDNF overexpression in muscle. Science 279, 1725-1729.
66. OPPENHEIM, R.W., HOUENOU, L.J., JOHNSON, J.E., LIN, L.-F.H., LI, L., LO, A.C., NEWSOME, A.L., PREVETTE, D.M., and WANG, S. (1995). Developing motor neurons rescued from programmed and axotomy-induced cell death by GDNF. Nature (London) 373, 344-346.
67. PARTRIDGE, T.A. (1991). Myoblast transfer. A possible therapy for inherited myopathies. Muscle Nerve 14, 197-212.
68. PARTRIDGE, T. (1994). Skeletal muscle as a target for gene therapy. Gene Ther. 1, 77-79.
69. PARTRIDGE, T.A., MORGAN, J.E., COULTON, G.R., HOFFMAN, E.P., and KUNKEL, L.M. (1989). Conversion of mdx myofibers from dystrophin-negative to -positive by injection of normal myoblasts. Nature (London) 337, 176-179.
70. PEAR, W.S., NOLAN, G.P., SCOTT, M.L., and BALTIMORE, D. (1993). Production of high-titer helper-free retroviruses by transient transfection. Proc. Natl. Acad. Sci. U.S.A. 90, 8392-8396.
71. PENNICA, D., ARCE, V., SWANSON, T.A., VEJSADA, R., POLLACK, R.A., ARMANINI, M., DUDLEY, K., PHILLIPS, H.S., ROSENTHAL, A., KATO, A.C., and HENDERSON, C.E. (1996). Cardiotrophin-1, a cytokine present in embryonic muscle, supports long-term survival of spinal motoneurons. Neuron 17, 63-74.
72. RANDO, T.A., and BLAU, H.M. (1994). Primary mouse myoblast purification, characterization and transplantation for cell-mediated gene therapy. J. Cell Biol. 125, 1275-1287.
73. ROSEN, D.R., SIDDIQUE, T., PATTERSON, D., FIGLEWICZ, D.A., SAPP, P., HENTATI, A., DONALDSON, D., GOTO, J., O'REGAN, G.P., DENG, H.X., RAHMANI, Z., KRIZUS, A., McKENNAYASEK, D., CAYABYAB, A., GASTON, S.M., BERGER, R., TANZI, R.E., HALPERIN, J.J., HERZFELDT, B., VAN DEN BERGH, R., HUNG, W.-Y., BIRD, T., DENG, G., MULDER, D.W., SMYTH, C., LAING, N.G., SORIANO, E., PERICAK-VANCE, M.A., HAINES, J., ROULEAU, G.A., GUSELLA, J.S., HORVITZ, H.R., and BROWN, R.H., JR. (1993). Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature (London) 362, 59-62.
74. SAGOT, Y., TAN, S.A., BAETGE, E., SCHMALBRUCH, I.I., KATO, A.C., and AEBISCHER, P. (1995). Polymer encapsulated cell lines genetically engineered to release ciliary neurotrophic factor can slow down progressive motor neuronopathy in the mouse. Eur. J. Neurosci. 7, 1313-1322.
75. SAGOT, Y., TAN, S.A., HAMMANG, J.P., AEBISCHER, P., and KATO, A.C. (1996). GDNF slows loss of motoneurons but not axonal degeneration or premature death of pmn/pmn mice. J. Neurosci. 16, 2335-2341.
76. SALVATORI, G., FERRARI, G., MEZZOGIORNO, A., SERVIDEI, S., COLETTA, M., TONALI, P., GIAVAZZI, R., COSSU, G., and MAVILIO, F. (1993). Retroviral vector-mediated gene transfer into human primary myogenic cells leads to expression in muscle fibers in vivo. Hum. Gene Ther. 4, 713-723.
77. SENDTNER, M. (1997). Gene therapy for motor neuron disease. Nature Med. 3, 380-381.
78. SIDDIQUE, T., PERICAK-VANCE, M.A., BROOKS, B.R., RODS, R.P., HUNG, W.-Y., ANTEL, J.P., MUNSAT, R.L., PHILLIPS, K., WARNER, K., SPEER, M., BIAS, W.B., SIDDIQUE, N.A., and ROSES, A.D. (1989). Linkage analysis in familial amyotrophic lateral sclerosis. Neurology 39, 919-925.
79. THOENEN, H., HUGHES, R.A., and SENDTNER, M. (1993). Trophic support of motoneurons: Physiological, pathophysiological and therapeutic implications. Exp. Neurol. 124, 47-55.
80. TSUKAGOSHI, H., YANAGISAWA, N., OGUCHI, K., NAGASHIMA, K., and MURAKAMI, T. (1979). Morphometric quantification of the cervical limb motor cells in controls and in amyotrophic lateral sclerosis. J. Neurol. Sci. 41, 287-297.
81. WALLACE, J.E., KRAUTER, E.E., and CAMPBELL, B.A. (1980). Motor and reflexive behavior in the aging rat. J. Gerontol. 35, 364-370.
82. WOLFF, J.A., MALONE, R.W., WILLIAMS, P., CHONG, W., ACSADI, G., JANI, A., and FELGNER, P.L. (1990). Direct gene transfer into mouse muscle in vivo. Science 247, 1465-1468.
83. WONG, P.C., PARDO, C.A., BORCHELT, D.R., LEE, M.K., COPELAND, N.G., JENKINS, N.A., SISODIA, S.S., CLEVELAND, D.W., and PRICE, D.L. (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.
84. YAN, Q., and MILLER, J.A. (1993). The use of trophic factors in degenerative motoneuron disease. Exp. Neurol. 124, 60-63.
85. YAN, Q., MATHESON, C., and LOPEZ, O.T. (1995). In vivo neurotrophic effects of GDNF on neonatal and adult facial motor neurons. Nature (London) 373, 341-344.
86. YANG, J., ONTELL, M.P., KELLY, R., WATKINS, S.C., and ONTELL, M. (1997). Limitations of nls β-galactosidase as a marker for studying myogenic lineage or the efficacy of myoblast transfer. Anat. Rec. 248, 40-50.