Mouse models of human lysosomal diseases

Brain Pathology

Volumn 8, Issue 1, 1998, Pages 195-215

  Suzuki, Kinuko ^a   Proia, Richard L ^b   Suzuki, Kunihiko ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA GALACTOSIDASE; BETA GALACTOSIDASE; BETA GLOBIN; BETA N ACETYLHEXOSAMINIDASE; BETA N ACETYLHEXOSAMINIDASE A; CARBOXYPEPTIDASE C; CERAMIDE TRIHEXOSIDE; CEREBROSIDE SULFATASE; GANGLIOSIDE GM2; GLOBOSIDE; GLUCOSYLCERAMIDASE; GLYCOLIPID; GLYCOSAMINOGLYCAN; HYDROLASE; LEVO IDURONIDASE; MIGLUSTAT; N ACETYLGALACTOSAMINE 4 SULFATASE; N4 (BETA N ACETYLGLUCOSAMINYL)ASPARAGINASE; OLIGOSACCHARIDE; PROTEIN PRECURSOR; RNA; SIALIC ACID; SIALIDASE; SPHINGOLIPID; SPHINGOLIPID ACTIVATOR PROTEIN; SPHINGOMYELIN PHOSPHODIESTERASE;

ANIMAL MODEL; ASPARTYLGLYCOSAMINURIA; BONE MARROW TRANSPLANTATION; CONFERENCE PAPER; FABRY DISEASE; GANGLIOSIDOSIS; GAUCHER DISEASE; GENE; HIGH PERFORMANCE THIN LAYER CHROMATOGRAPHY; HUMAN; LYSOSOME STORAGE DISEASE; MAROTEAUX LAMY SYNDROME; METACHROMATIC LEUKODYSTROPHY; MUCOPOLYSACCHARIDOSIS; NIEMANN PICK DISEASE; NONHUMAN; NORTHERN BLOTTING; ORAL DRUG ADMINISTRATION; SANDHOFF DISEASE; STEM CELL; TAY SACHS DISEASE;

EID: 0031983745     PISSN: 10156305     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1750-3639.1998.tb00145.x     Document Type: Conference Paper

References (97)

1. Alroy J, Orgad U, DeGasperi R, Richard R, Warren K, Knowles JG, Thalhammer JG, Raghavan SS (1992) Canine GM1-gangliosidosis: a clinical, morphologic, histochemical and biochemical comparison of two different models. Am J Pathol 140: 675-689
2. Alroy J, Warren CD, Raghavan SS, Kolodny EH (1989) Animal models for lysosomal storage diseases: Their past and future contribution. Hum Pathol 20: 823-826
3. Baker HJ, Mote JA, Linsey JR, Creel RM (1982) Animal models of human ganglioside storage diseases. Fed Proc 35: 1193-1201
4. Bapat B, Ethier M, Neote K, Mahuran D, Gravel RA (1988) Cloning and sequence of a cDNA encoding the β subunit of mouse β-hexosaminidase. FEBS Lett 237: 191-195
5. Beutler E, Grabowski GA (1995) Gaucher Disease. In: Metabolic and Molecular Basis of Inherited Disease, 7th Edition, Scriver CR, Beaudet AL, Sly WS, Valle D (eds.), Chapter 86, pp. 2641-2670, McGraw-Hill: New York.
6. Beccari T, Hoade J, Oriacchio J, Stirling JL (1992) Cloning and sequence analysis of a cDNA encoding the a subunit of mouse β-N-acetylhexosaminidase and comparison with the human enzyme. Biochem J 285: 593-596
7. Birkenmeier EH, Davisson MT, Beamer WG, Ganschow RE, Vogler CA, Gwynn B, Lyford KA, Maltais LM, Wawrzyniak CJ (1989) Murine mucopolysaccharidosis type VII. Characterization of a mouse with β-glucuronidase deficiency. J Clin Invest 83: 1258-1266
8. Boustany RM, Qian WH, Suzuki K (1993) Mutations in the lysosomal β-galactosidase cause GM1 gangliosidosis in American patients. Am J Hum Genet 53: 881-888
9. Bradova R Ulrich-Bott B, Roggendorf W, Paton BC, Harzer K (1993) Prosaposin deficiency: Further characterization of the sphingolipid activator protein-deficient sibs. Multiple glycolipid elevations (including lactosylceramidosis), partial enzyme deficiencies and ultrastructure of the skin in this generalized sphingolipid storage disease. Hum Genet 92: 143-152
10. M2 degradation by β-hexosaminidase isoenzymes in tissue extracts from different species. Hoppe-Seyler Z Physiol Chem 364: 821-829
11. Chakraborty S, Rafi MA, Wenger DA (1994) Mutations in the lysosomal β-galactosidase gene that cause the adult form of GM1-gangliosidosis. Am J Hum Genet 54: 1004-1013
12. Clarke LA, Russell CS, Pownall S, Warrington CL, Borowski A, Dimmick JE, Toone J, Jirik FR (1997) Murine mucopolysaccharidosis type I: targeted disruption of the murine α-L-iduronidase gene. Hum Mol Genet 6: 503-511
13. Cohen-Tannoudji M, Marchand P, Akli S, Sheardown SA, Puech J-P, Kress C, Gressens P, Nassogne M-C, Beccari T, Muggleton-Harris AL, Evrard P, Stirling JL, Poenaru L, Babinet C (1995) Disruption of murine HEXA gene leads to enzymatic deficiency and to neuronal lysosomal storage, similar to that observed in Tay-Sachs disease. Mam Genome 6: 844-849
14. d'Azzo A, Andrea G, Strisciugtio P, Galjaard H (1995) Galactosialidosis. In: The Metabolic and Molecular Basis of Inherited Disease, 7th Edition., Scriver CR, Beaudet AL, Sly WS, Valle D (eds.), Chapter 91, pp. 2825-2838, McGraw-Hill: New York.
15. Desnick RJ, Ioannou YA, Eng CM (1995) α-Galactosidase A deficiency: Fabry disease. In : The Metabolic and Molecular Basis of Inherited Disease, 7th Edition, Scriver CR, Beaudet AL, Sly WS, Valle D (eds.), Chapter 89, pp. 2741-2784, McGraw-Hill: New York
16. de Veber GA, Schwarting GA, Kolodny EH, Kowall NW (1992) Fabry disease. Immunochemical characterization of neuronal involvement. Ann Neurol 31: 409-415
17. Di Natale P, Annella T, Daniele A, Spagnuolo G, Cerundolo R, De Caprariis D, Gravino AE (1992) Animal models for lysosomal storage disease: a new case of feline mucopolysaccharidosis VI. J Inher Metab Dis 15: 17-24
18. Evers M, Saftig P, Schmidt P, Hafner A, McLoghlin DB, Schmahl WS, Hess B, von Figura K, Peters C (1996) Targeted disruption of the arylsulfatase B gene results in mice resembling the phenotype of mucopolysaccharodosis VI. Proc Natl Acad Sci USA 93: 8214-8219
19. Fujita N, Suzuki K, Vanier M, Popko B, Maeda N, Klein A, Henseler M, Sandhoff K, Nakayasu H, Suzuki K (1996) Targeted disruption of the mouse sphingohpid activator protein gene: a complex phenotype, including severe leukodystrophy and wide-spread storage of multiple sphingolipids. Hum Mol Genet 5: 711-725
20. Gieselmann V, Zlotogora J, Harris A, Wenger DA. Morris CP (1994) Molecular genetics of metachromatic leukodystrophy. Hum Mutat 4: 233-242
21. M2 gangliosidosis. In : The Metabolic and Molecular Basis of Inherited Disease, 7th Edition, Scriver CR, Beaudet AL, Sly WS, Valle D (eds.), Chapter 92, pp. 2839-2879, McGraw-Hill: New York
22. Gregoire A, Perier O, Dustin P (1966) Metachromatic ieukodystrophy, an electron microscopic study. J Neuropathol Exp Neurol 25: 617-636
23. Grosveld F, van Assendelft G B, Greaves DR, Kollias G (1987) Position-independent, high level expression of the human β-globin gene in transgenic mice. Cell 51: 975-985.
24. Hahn CN, del Pilar Martin M, Schröder M, Vanier MT, Hara Y, Suzuki K, Suzuki K, d'Azzo A. (1997) Generalized CMS disease and massive GM1-ganglioside accumulation in mice defective in lysosomal acid β-galactosidase. Hum Mol Genet 6: 205-211
25. Harzer K, Paton SC, Poulos A, Kustermanrt-Kuhn B, Roggendorf W, Grisar T, Popp M (1989) Sphingolipid activator deficiency in a 16 week old atypical Gaucher disease patient and his fetal sibling: Biochemical signs of combined sphingolipidoses. Eur J Pediatr 149: 31-39
26. Haskins M, Baker HJ, Birkenmeier E, Hoogerbrugge P, Poorthuis B, Sakiyama T, Shull R, Taylor RM, Thrall M, Walkley SU (1991) Transplantation in animal model systems. In: Treatment of genetic diseases. Desnick RJ (ed.), pp. 183-201, Churchill Livingstone: Edinburgh, London
27. Haskins ME, Desnick RJ, DiFerrante N, Jezyik PF, Patterson DF (1984) β-glucuronidase deficiency in a dog. A model of human mucopolysaccharidosis VII. Pediatr Res 18: 980-984
28. Haskins ME, Jezyk PF, Desnick RJ, McDonough SK, Patterson DF (1979) α -L-iduronidase deficiency in a cat: A model of mucopolysaccharidoses I. Pediatr Res 13: 1294-1297
29. Hess B, Saftig P, Hartmann D, Coenen R, Lüllmann-Rauch R, Goebel HH, Evers M, von Figura K, D'Hooge R, Nagels G, De Deyn P, Peters C, Gieselmann V (1996) Phenotype of arylsulfatase A-deficient mice: relationship to human metachromatic leukodystrophy. Proc Natl Acad Sci USA 93: 14821-14828
30. Ho MW, O'Brien JS (1971) Gaucher's disease: deficiency of "acid" β-glucosidase and reconstitution of enzyme activity in vitro. Proc Natl Acad Sci USA 68: 2810-2813
31. Holleran WM, Ginns El, Menon GK, Grundmann J-U, Fartasch M, McKinney CE, Elias PM, Sidransky E. (1994) Consequences of β-glucocerebrosidase deficiency in epidermis : ultrastructure and permeability barrier alteration in Gaucher disease. J Clin Invest 91: 1736-1764
32. Hoogerbrugge PM, Suzuki K, Suzuki K, Poorthuis BJHM, Kobayashi T, Wagemaker G, van Bekkum DW (1988) Donor derived cells in the central nervous system of twitcher mice after bone marrow transplantation. Science 239: 1035-1038
33. Horinouchi K, Erlich S, Peri DP, Ferlinz K, Bisgaier CL, Sandhoff K, Desnick RJ, Stewart CL, Schuchman EH (1995) Acid sphingomyelmase deficient mice: a model of type A and B Niemann-Pick disease. Nature Genet 10: 288-293
34. Jezyk PF, Haskins ME, Patterson DF, Mellman WJ, Greenstein M (1977) Mucopolysaccharidosis in a cat with arylsulfatase B deficiency. A model of Maroteaux-Lamy syndrome. Science 198: 834-836
35. Kaartinen V, Mononen I, Voncken JW, Noronkoski T, Gonzalez-Gomez, Heisterkamp N and Groffen J (1996) A mouse model for the human lysosomal disease aspartylglucosaminuria. Nature Med 2: 1375-1378
36. Kolodny EH, Fluharty AL (1995) Metachromatic leukodystrophy and multiple sulfatase deficiency: sulfatide lipidosis. In: The Metabolic and Molecular Basis of inherited Diseases, 7th Edition, Scriver CR, Beaudet AL. Sly WS, Valle D (eds.). Chapter 88, pp. 2693-2739, McGraw-Hill: New York
37. Kuemmel TA, Schroeder R, Stoffel W (1997) Light and electron microscopic analysis of the central and peripheral nervous systems of acid sphingomyelinase-deficient mice resulting from gene targeting. J Neuropathol Exp Neurol 56: 171-179
38. Leinekugel P, Michel S, Conzelmann E, Sandhoff K (1992) Quantitative correlation between the residual activity of β-hexosaminidase A and aryisulfatase A and the severity of the resulting lysosomal storage disease. Hum Genet 88: 513-523
39. Liu Y, Hoffmann A, Grinberg A, Westphal H, McDonald MP, Miller KM, Crawley JN, Sandhoff K, Suzuki K, Proia RL (1997) Mouse model of GM2 activator deficiency manifests cerebellar pathology and motor impairment. Proc Natl Acad Sci USA 94: 8138-8143
40. Luzi P, Rafi MA, Victoria T, Baskin GB, Wenger DA (1997) Characterization of the rhesus monkey galactocerebrosidase (GALC) cDNA and gene and identification of the mutation causing goboid cell leukodystrophy (Krabbe disaes) in the primate. Genomics 42: 319-324
41. Matsuda J, Suzuki O, Oshima A, OguraA, Naiki M, Suzuki Y (1997) Neurological manifestations of knockout mice with b-galactosidase deficiency. Brain Dev 19: 19-20
42. Matsumoto A, Vanier MT, Oya Y, Kelly D, Popko B, Wenger DA, Suzuki K, Suzuki K (1998) Minimal increment in galactosylceramidase expression is sufficient for significant phenotypic improvement in twitcher mouse. Dev Brain Dysfunct, in press
43. Matsushima G, Taniike M, Glimcher LH, Grusby MJ, Frelinger JA, Suzuki K, Ting J P-Y (1994) Absence of MHC Class II molecules reduces CNS demyelination, microglial/macrophages infiltration, and twitching in murine gioboid cell leukodystrophy. Cell 78: 645-656
44. Mehl E, Jatzkewitz H (1964) Eine Cerebrosidsulfatase aus Schweineniere. Hoppe-Seylers Z Physiol Chem 339: 260-276
45. Miranda SRP, Erlich S, Visser JWM, Gatt S, Dagan A, Friedrich VL Jr, Schuchman EH (1997) Bone marrow transplantation in acid sphingomyelinase-deficient mice: engraftment and cell migration into the brain as a function of radiation, age. and phenotype. Blood 90: 444-452
46. M2-Gangliosidosis (Sandhoff Disease). Am J Pathol 144: 1109-1118
47. Neufeld EF, Muenzer J (1995) The Mucopolysaccharidoses In: The Metabolic and Molecular Basis of Inherited Diseases, 7th Edition, Scriver CR, Beaudet AL, Sly WS, Valle D (eds.), Chapter 78, pp. 2465-2494, McGraw-Hitl: New York
48. M1 gangliosidosis (genetic β-galactosidase deficiency): identification of four mutations in different clinical phenotypes among Japanese patients. Am J Hum Genet 49: 566-574
49. Nordborg C, Kyllerman M, Conradi N, Mansson J-E (1997) Early-infantile galactosialidosis with multiple brain infarctions morphological, neuropathological and neurochemical findings. Acts Neuropathol (Bert) 93: 24-33
50. Norflus FN, McDonald MP, Crawley JN, Suzuki K, Proia RL, Tifft CJ (1996) Bone marrow transplantation as a therapy for GM2 gangliosidosis Am J Hum Genet 59: A204
51. Onshima T, Murray GJ, Swaim WD, Longenecker G, Quirk JM, Cardarelli CO, Sugimoto Y Pastan I, Gottesman MM, Brady RO, Kulkarni AB (1997) α-galactosidase A deficient mice: a model of Fabry disease. Proc Natl Acad Sci USA 94: 2540-2544
52. Otterbach B, Stoffel W (1995) Acid sphingomyelinase-deficient mice mimic the neurovisceral form of human lysosomal storage disease (Niemann-Pick disease). Cell 81: 1053-1061
53. Oya Y, Nakayasu H, Fujita N, Suzuki K, Suzuki K. Pathological study of mice with total deficiency of sphingolipid activator proteins (SAP knockout mice). Acta Neuropathol (Berl), submitted
54. Oyanagi K, Ohama E, Miyashita K, Yoshino H, Miyatake T, Yamazaki M. Ikuta F (1991) Galactosialidosis: neuropathological findings in a case of the late infantile type. Acta Neuropathol (Berl) 82: 331-339
55. Peng L, Suzuki K (1987) Ultrastructural study of neurons in metachromatic leukodystrophy. Clin Neuropathol 6: 224-230
56. Phaneuf D, Wakamatsu N, Huang J-Q, Borowski A, Peterson AC, Fortunate SR, Ritter G, Igdoura SA, Morales CR, Benoit G, Akerman BR, Leclerc D, Hanai N, Martin JD, Trasler JM, Gravel RA. (1996) Dramatically different phenotypes in mouse models of human Tay-Sachs and Sandhoff diseases Hum Mot Genet 5: 1-14
57. Platt FM, Neises GR, Reinkensmeier G, Townsend MJ, Perry VH, Proia R, Winchester B, Dwek RA, Butters TD (1997) Prevention of lysosomal storage in Tay-Sachs mice treated with N-Butyldeoxynojirimycin. Science 276: 428-431
58. Rahman AN, Lindenberg R. (1963) The neuropathology of hereditary dystrophic lipidosis. Arch Neurol 9: 373-385
59. Sands MS, Vogler C, Torrey A, Levy B, Gwynn B, Grubb J, Sly WS, Birkenmeier EH (1997) Murine mucopolysaccharidosis type VII. longterm therapeutic effects of enzyme replacement and enzyme replacement following by bone marrow transplantation. J Clin Invest 99: 1596-1605
60. Sango K, McDonald MP, Crawley JN, Mack ML, Tifft CJ, Stop E, Starr CM, Hoffmann A, Sandnoff K, Suzuki K, Proia RL. (1996) Mice lacking both subunits of lysosomal β-hexosaminidase display gangliosidosis and mucopolysaccharidosis. Nature Genet 14: 348-352
61. Sango K, Yamanaka S, Hoffmann A, Okuda Y, Grinberg A, Westphal H, McDonald MP, Crawley JN, Sandhoff K, Suzuki K, Proia RL. (1995) Mouse models of Tay-Sachs and Sandhoff diseases differ in neurologic phenotype and ganghoside metabolism. Nature Genet 11: 170-176
62. Sandhoff K, Harzer K, Fürst W (1995) Sphingolipid activator proteins In: The Metabolic and Molecular Basis of Inherited Diseases. 7th Edition, Scriver CR, Beaudet AL, Sly WS, Valle D (eds.), Chapter 76, pp. 2427-2441, McGraw Hill: New York
63. Schnabel D, Schröder M, Fürst M, Klein A, Hurwitz R, Zenk T, Weber J, Harzer K, Paton BC, Poulos A, Suzuki K, Sandhoff K (1992) Simultaneous deficiency of sphingolipid activator proteins 1 and 2 is caused by a mutation in the initiation codon of their common gene. J Biol Chem 267: 3312-3315
64. Schuchman EH, Desnick RJ (1995) Niemann-Pick disease type A and B: acid sphingomyelinase deficiencies. In: The Metabolic and Molecular Basis of Inherited Diseases, 7th Edition, Scriver CR, Beaudet AL, Sly WS, Valle D (eds.), Chapter 84, pp. 2601-2624, McGraw-Hill: New York
65. Scott HS, Bunge S, Gal A, Clarke LA, Morris CP, Hopwood JJ (1995) Molecular genetics of mucopolysaccharidosis type I: diagnostic, clinical and biological implications. Hum Mutat 6: 288-302
66. Shull RM, Helman RG, Spellacy E, Constantopoulos G, Munger RJ, Neufeld EF (1984) Morphologic and biochemical studies of canine mucopolysaccharidosis I. Am J Pathol 114: 487-495
67. Sidransky E, Fartasch M, Lee RE, Metlay LA, Abella S, Zimran A, Gao W, Elias PM, Ginns El, Holleran WM (1996) Epidermal abnormalities may distinguish type 2 from type 1 and 3 of Gaucher disease. Pediatr Res 39: 134-141
68. Sidransky E, Sherer DM, Ginns El (1992) Gaucher disease in the neonate: A distinct Gaucher phenotype is analogous to a mouse model created by targeted disruption of the glucocerebrosidase gene. Pediatr Res 32: 494-498
69. Sung JH (1979) Autonomic neurons affected by lipid storage in the spinal cord in Fabry's disease: distribution of autonomic neurons in the sacral cord. J Neuropathol Exp Neurol 38: 87-98
70. Suzuki K (1968) Cerebral GM1-gangliosidosis: chemical pathology of visceral organs. Science 159: 1471-1472
71. Suzuki K (1991) Neuropathology of late onset gangliosidosis: a review. Dev Neurosci 13: 205-210
72. Suzuki K (1994) A genetic demyelinating disease globoid cell leukodystrophy: studies with animal models. J Neuropath Exp Neurol 53: 359-363
73. Suzuki K, Sango K, Proia RL, Langaman CL (1997) Mice deficient in all forms of lysosomal β-hexosaminidase show mucopolysaccharidosis-like pathology. J Neuropathol Exp Neurol 56: 693-703
74. Suzuki K, Suzuki K (1996) The gangliosidoses. In: Handbook of Clinical Neurology, Vinken PJ, Bruyn GW (eds.) Vol 66, revised Series 22: Neurodystrophies and Neurolipidoses, Moser H (volume ed.), pp. 247-280, Elsevier Science Publishers: Amsterdam
75. M1-gangliosidosis. Hum Genet 91: 407
76. Suzuki Y, Sakuraba H, Oshima A (1995) β-galactosidase deficiency (β-galactosidosis): GM1 gangliosidosis and Morquio B disease. In: The Metabolic and Molecular Basis of Inherited Disease, 7th Edition, Scriver CR, Beaudet AL, Sly WS, Valle D (eds.). Chapter 90, pp. 2785-2824, McGraw-Hill: New York
77. Taniike M, Yamanaka S, Praia RL, Langaman CL, Bone-Turrentine T, Suzuki K (1995) Neuropathology of mice with targeted disruption of Hexa gene, a model of TaySachs disease. Acta Neumpathol (Berl) 89: 296-304
78. Terry RD, Korey SR (1960) Membranous cytoplasmic granules in infantile amaurotic idiocy Nature 188: 1000-1002
79. Terry RD, Weiss M (1963) Studies in Tay-Sachs disease: II. Ultrastructure of cerebrum. J Neuropathol Exp Neurol 22:18-55
80. Thomas GH, Beaudet AL (1995) Disorders of glycoprotein degradation and structure: α-mannosidosis, β-mannosidosis, fucosidosis, scialidosis, aspartylglucosaminuria, and carbohydrate-deficient glycoprotein syndrome. In: The Metabolic and Molecular Basis of Inherited Disease, 7th Edition, Scriver CR, Beaudet AL, Sly WS, Valle D (eds.), Chapter 81, pp. 2529-2561, McGraw-Hill: New York
81. Thompson JN, Jones MZ, Dawson G, Huffman PS (1992) N-acetylglucosamine 6 suifatase deficiency in a Nubian goat: A model of Sanfilippo syndrome type D (mucopolysaccharidosis HID) J inher Metab Dis 15: 760-768
82. Tybulewicz VLJ, Tremblay ML, LaMarca ME, Willemsen RW, Stubblefield BK, Winfield S, Zablocka B, Sidransky E, Martin BM, Huang SP, Mintzer KA, Westphal H, Mulligan RC, Ginns El (1992) Animal model of Gaucher's disease from targeted disruption of the mouse glucocerebrosidase gene. Nature 357: 407-410
83. Vanier MT, Suzuki K (1996) Niemann-Pick disease. In: Handbook of Clinical Neurology, Vinken PJ, Bruyn GW (eds.), Vol. 66. revised Series 22: Neurodystrophies and Neurolipidoses, Moser H (volume ed.), pp. 133-162, Elsevier Science Publishers: Amsterdam
84. Von Hirsch T, Peiffer J (1955) Über histologische Methoden in der Differentialdiagnose von Leukodystrophien und Lipidosen. Arch Psychiatr Nervenkr 194: 88-104
85. Walkley SU (1988) Pathobiology of neuronal storage disease. Int Rev Neurobiol 29: 191-244
86. Walkley SU, Thrall MA, Dobrenis K, Huang M, March PA, Siegel DA, Wurzelmann S (1994) Bone marrow transplantation corrects the enzyme defect in neurons of the central nervous system in a lysosomal storage disease. Proc Natl Acad Sci USA 91: 2970-2974
87. Wang AM, Stewart CL, Desnick RJ (1993) α-N-Acetylgalactosaminidase: characterization of the murine cDNA and genomic sequences and generation of the mice by targeted gene disruption, (abstract). Am J Hum Genet 53: 99
88. Wenger DA, Tarby TJ, Wharton C (1978) Macular cherryred spots and myoclonus with dementia: Coexistent neuraminidase and β-galactosidase deficiencies. Biochem Biophys Res Commun 82: 589-595
89. Willemsen R, Tybulewicz E, Stdransky E, Eliason WK, Martin BM, LaMarca ME, Reuser AJJ, Tremblay M, Westphal H, Mulligan RC, Ginns El (1995) A biochemical and ultrastructural evaluation of the type 2 Gaucher mouse. Mol Chem Neuropathol 24: 179-192
90. Wolf HJ, Pietra GG (1964) The visceral lesions of metachromatic leukodystrophy. Am J Pathol 44: 921-930
91. Yamanaka S, Johnson MD, Grinberg A, Westphal H, Crawley JN, Taniike M, Suzuki K, PrOia RL (1994) Targeted disruption of the Hexa gene results in mice with biochemical and pathologic features of Tay-Sachs disease. Proc Natl Acad Sci USA 91: 9975-9979
92. Yamanaka S, Johnson ON, Norflus F, Boles DJ, Proia RL (1994) Structure and expression of the mouse β-hexosaminidase genes, Hexa and Hexb. Genomics 21: 588- 596
93. Yamano T, Shimada M, Sugino H, Dezawa T, Koike M, Okada S, Yabuuchi H (1985) Ultrastructural study on a severe infantile sialidosis (β-galactosidase-α-neuraminidase deficiency). Neuropediatrics 16: 109-112
94. Yeager AM, Brennan S, Tiffany C, Moser HW, Santos CW (1984) Prolonged survival and remyelination after hematopoietic cell transplantation in the twitcher mouse. Science 225: 1052-1054
95. Yeager AM, Shinn C, Shinohara M, Pardoll DM (1993) Hematopoietic cell transplantation in the twitcher mouse: The effects of pretransplant conditioning with graded doses of Busulfan. Transplantation 56: 185-190
96. Yoshida M, Ikadai A, Maekawa A, Takahashi M, Nagase S (1993) Pathological characteristics of mucopolysaccharidosis VI in the rat. J Comp Pathol 109 :141-153
97. Zhou XY, Morreau H, Rottier R, Davis D, Bonten E, Gillemans N, Wenger D, Grosveld FG, Doberty P, Suzuki K, Grosveld GC, d'Azzo A (1995) Mouse model for the lysosomal disorder galactosialidosis and correction of the phenotype with overexpressing erythroid precursor cells. Genes Dev 9: 2623-2634