Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Genetically engineered mouse models of neurodegenerative diseases

Nature Neuroscience volume 5, pages 633–639 (2002)Cite this article

Abstract

Recent research has significantly advanced our understanding of the molecular mechanisms of neurodegenerative diseases, including Alzheimer's disease (AD) and motor neuron disease. Here we emphasize the use of genetically engineered mouse models that are instrumental for understanding why AD is a neuronal disease, and for validating attractive therapeutic targets. In motor neuron diseases, Cu/Zn superoxide dismutase and survival motor neuron mouse models are useful in testing disease mechanisms and therapeutic strategies for amyotrophic lateral sclerosis (ALS) and spinal motor atrophy, respectively, but the mechanisms that account for selective motor neuron loss remain uncertain. We anticipate that, in the future, therapies based on understanding disease mechanisms will be identified and tested in mouse model systems.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Pathological features of Alzheimer's disease.

Bob Crimi

Figure 2: Amyloid precursor protein (APP) and secretase cleavages.

Amy Center

Similar content being viewed by others

References

  1. Price, D.L., Tanzi, R.E., Borchelt, D.R. & Sisodia, S.S. Alzheimer's disease: genetic studies and transgenic models. Annu. Rev. Genet. 32, 461–493 (1998).

    CAS  PubMed  Google Scholar 

  2. Lee, V.M.Y. & Trojanowski, J.Q. Neurodegenerative taupathies: human disease and transgenic mouse models. Neuron 24, 507–510 (1999).

    CAS  PubMed  Google Scholar 

  3. Lin, X., Cummings, C.J. & Zoghbi, H.Y. Expanding our understanding of polyglutamine diseases through mouse models. Neuron 24, 499–502 (1999).

    CAS  PubMed  Google Scholar 

  4. Dunnett, S.B. & Bjorklund, A. Prospects for new restorative and neuroprotective treatments in Parkinson's Disease. Nature 399, A32–A39 (1999).

    CAS  PubMed  Google Scholar 

  5. Yamamoto, A., Lucas, J.J. & Hen, R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell 101, 57–66 (2000).

    CAS  PubMed  Google Scholar 

  6. Hardy, J. & Gwinn-Hardy, K. Genetic classification of primary neurodegenerative disease. Science 282, 1075–1079 (1998).

    CAS  PubMed  Google Scholar 

  7. Selkoe, D.J. Alzheimer's disease: genes, proteins and therapy. Physiol. Rev. 81, 741–766 (2001).

    CAS  PubMed  Google Scholar 

  8. Price, D.L., Sisodia, S.S. & Borchelt, D.R. Genetic neurodegenerative diseases: the human illness and transgenic models. Science 282, 1079–1083 (1998).

    CAS  PubMed  Google Scholar 

  9. Schilling, G. et al. Intranuclear inclusions and neuritic pathology in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum. Mol. Genet. 8, 397–407 (1999).

    CAS  PubMed  Google Scholar 

  10. Goedert, M., Spillantini, M.G. & Davies, S.W. Filamentous nerve cell inclusions in neurodegenerative diseases. Curr. Opin. Neurobiol. 8, 619–632 (1998).

    CAS  PubMed  Google Scholar 

  11. Zoghbi, H.Y. & Orr, H.T. Polyglutamine diseases: protein cleavage and aggregation. Curr. Opin. Neurobiol. 9, 566–570 (1999).

    CAS  PubMed  Google Scholar 

  12. Albert, M.S. & Drachman, D.A. Alzheimer's disease. What is it, how many people have it, and why do we need to know? Neurology 55, 166–168 (2000).

    CAS  PubMed  Google Scholar 

  13. Mesulam, M.M. Neuroplasticity failure in Alzheimer's disease: bridging the gape between plaques and tangles. Neuron 24, 521–529 (1999).

    CAS  PubMed  Google Scholar 

  14. Price, D.L. & Sisodia, S.S. Mutant genes in familial Alzheimer's disease and transgenic models. Annu. Rev. Neurosci. 21, 479–505 (1998).

    CAS  PubMed  Google Scholar 

  15. Beach, T.G. et al. The cholinergic deficit coincides with Aβ deposition at the earliest histopathologic stages of Alzheimer disease. J. Neuropathol. Exp. Neurol. 59, 308–313 (2000).

    CAS  PubMed  Google Scholar 

  16. Serpell, L.C., Blake, C.C.F. & Fraser, P.E. Molecular structure of a fibrillar Alzheimer's Aβ fragment. Biochemistry 39, 13269–13275 (2000).

    CAS  PubMed  Google Scholar 

  17. Lansbury, P.T. Jr. Evolution of amyloid: what normal protein folding may tell us about fibrillogenesis and disease. Proc. Natl. Acad. Sci. USA 96, 3342–3344 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Tanzi, R.E. New frontiers in Alzheimer's disease genetics. Neuron 32, 181–184 (2001).

    CAS  PubMed  Google Scholar 

  19. Selkoe, D.J. Clearing the brain's amyloid cobwebs. Neuron 32, 177–180 (2001).

    CAS  PubMed  Google Scholar 

  20. Sinha, S. et al. Purification and cloning of amyloid precursor protein β-secretase from human brain. Nature 402, 537–540 (1999).

    CAS  PubMed  Google Scholar 

  21. Hussain, I. et al. Identification of a novel aspartic protease (Asp 2) as β-secretase. Mol. Cell. Neurosci. 14, 419–427 (1999).

    CAS  PubMed  Google Scholar 

  22. Lin, X. et al. Human aspartic protease memapsin 2 cleaves the β-secretase site of β-amyloid precursor protein. Proc. Natl. Acad. Sci. USA 97, 1456–1460 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Yan, R. et al. Membrane-anchored aspartyl protease with Alzheimer's disease β-secretase activity. Nature 402, 533–537 (1999).

    CAS  PubMed  Google Scholar 

  24. Vassar, R. et al. β-secretase cleavage of Alzheimer's amyloid precusor protein by the transmembrane aspartic protease BACE. Science 286, 735–741 (1999).

    CAS  PubMed  Google Scholar 

  25. Wong, P.C., Price, D.L. & Cai, H. The brain's susceptibility to amyloid plaques. Science 293, 1434–1435 (2001).

    CAS  PubMed  Google Scholar 

  26. Farzan, M., Schnitzler, C.E., Vasilieva, N., Leung, D. & Choe, H. BACE2, a β-secretase homolog, cleaves at the β site and within the amyloid-β region of the amyloid-β precursor protein. Proc. Natl. Acad. Sci. USA 97, 9712–9717 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Nilsberth, C. et al. The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Aβ protofibril formation. Nat. Neurosci. 4, 887–893 (2001).

    CAS  PubMed  Google Scholar 

  28. Sherrington, R. et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 375, 754–760 (1995).

    CAS  PubMed  Google Scholar 

  29. Levy-Lahad, E. et al. Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science 269, 973–977 (1995).

    CAS  PubMed  Google Scholar 

  30. Rogaev, E.I. et al. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature 376, 775–778 (1995).

    CAS  PubMed  Google Scholar 

  31. Thinakaran, G. et al. Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17, 181–190 (1996).

    CAS  PubMed  Google Scholar 

  32. Sisodia, S.S. & George-Hyslop, P.H. gamma-secretase, Notch, Aβ and Alzheimer's disease: where do the presenilins fit in? Nat. Rev. Neurosci. 3, 281–290 (2002).

    CAS  PubMed  Google Scholar 

  33. Esler, W.P. & Wolfe, M.S. A portrait of Alzheimer secretases—new features and familiar faces. Science 293, 1449–1454 (2001).

    CAS  PubMed  Google Scholar 

  34. Vassar, R. & Citron, M. Aβ-generating enzymes: recent advances in β- and γ-secretase research. Neuron 27, 419–422 (2000).

    CAS  PubMed  Google Scholar 

  35. De Strooper, B. et al. Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391, 387–390 (1998).

    CAS  PubMed  Google Scholar 

  36. Wolfe, M.S. et al. Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and secretase activity. Nature 398, 513–517 (1999).

    CAS  PubMed  Google Scholar 

  37. Kopan, R. & Goate, A. Aph-2/Nicastrin: an essential component of gamma-secretase and regulator of notch signaling and presenilin localization. Neuron 33, 321–324 (2002).

    CAS  PubMed  Google Scholar 

  38. Calhoun, M.E. et al. Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid. Proc. Natl. Acad. Sci. USA 96, 14088–14093 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Chen, G. et al. A learning deficit related to age and β-amyloid plaques in a mouse model of Alzheimer's disease. Nature 408, 975–979 (2000).

    CAS  PubMed  Google Scholar 

  40. Mucke, L. et al. High-level neuronal expression of Aβ1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J. Neurosci. 20, 4050–4058 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Hsia, A.Y. et al. Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. Proc. Natl. Acad. Sci. USA 96, 3228–3233 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Lewis, J. et al. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 293, 1487–1491 (2001).

    CAS  PubMed  Google Scholar 

  43. Götz, J., Chen, F., Barmettler, R. & Nitsch, R.M. Tau filament formation in transgenic mice expressing P301L tau. J. Biol. Chem. 276, 529–534 (2001).

    PubMed  Google Scholar 

  44. Borchelt, D.R. et al. Accelerated amyloid deposition in the brains of transgenic mice co-expressing mutant presenilin 1 and amyloid precursor proteins. Neuron 19, 939–945 (1997).

    CAS  PubMed  Google Scholar 

  45. Zheng, H. et al. β-amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell 81, 525–531 (1995).

    CAS  PubMed  Google Scholar 

  46. Heber, S. et al. Mice with combined gene knock-outs reveal essential and partially redundant functions of amyloid precursor protein family members. J. Neurosci. 20, 7951–7963 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Struhl, G. & Greenwald, I. Presenilin is required for activity and nuclear access of notch in drosophila. Nature 398, 522–525 (1999).

    CAS  PubMed  Google Scholar 

  48. Wong, P.C. et al. Presenilin 1 is required for Notch1 and Dll1 expression in the paraxial mesoderm. Nature 387, 288–292 (1997).

    Article  CAS  PubMed  Google Scholar 

  49. Donoviel, D. et al. Mice lacking both presenilin genes exhibit early embryonic patterning defects. Genes Dev. 13, 2801–2810 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Yu, H. et al. APP processing and synaptic plasticity in presenilin-1 conditional knockout mice. Neuron 31, 713–726 (2001).

    CAS  PubMed  Google Scholar 

  51. Feng, R. et al. Deficient neurogenesis in forebrain-specific presenilin-1 knockout mice is associated with reduced clearance of hippocampal memory traces. Neuron 32, 911–926 (2001).

    CAS  PubMed  Google Scholar 

  52. Cai, H. et al. BACE1 is the major β-secretase for generation of Aβ peptides by neurons. Nat. Neurosci. 4, 233–234 (2001).

    CAS  PubMed  Google Scholar 

  53. Luo, Y. et al. Mice deficient in BACE1, the Alzheimer's β-secretase, have normal phenotype and abolished β-amyloid generation. Nature 4, 231–232 (2001).

    CAS  Google Scholar 

  54. Roberds, S.L. et al. BACE knockout mice are healthy despite lacking the primary β-secretase activity in brain: implication for Alzheimer's disease therapeutics. Hum. Mol. Genet. 10, 1317–1324 (2001).

    CAS  PubMed  Google Scholar 

  55. Bodendorf, U., Fischer, F., Bodian, D., Multhaup, G. & Paganetti, P. A splice variant of β-secretase deficient in the amyloidogenic processing of the amyloid precursor protein. J. Biol. Chem. 276, 12019–12023 (2001).

    CAS  PubMed  Google Scholar 

  56. Li, Y.M. et al. Photoactivated γ-secretase inhibitors directed to the active site convalently label presenilin 1. Nature 405, 689–693 (2000).

    CAS  PubMed  Google Scholar 

  57. Huppert, S.S. et al. Embryonic lethality in mice homozygous for a processing-deficient allele of Notch 1. Nature 405, 966–970 (2000).

    CAS  PubMed  Google Scholar 

  58. Petit, A. et al. New protease inhibitors prevent γ-secretase-mediated production of Aβ40/42 without affecting Notch clevage. Nat. Cell Biol. 3, 507–511 (2001).

    CAS  PubMed  Google Scholar 

  59. Hadland, B.K. et al. γ-secretase inhibitors repress thymocyte development. Proc. Natl. Acad. Sci. USA 98, 7487–7491 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Bard, F. et al. Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer's disease. Nat. Med. 6, 916–919 (2000).

    CAS  PubMed  Google Scholar 

  61. Schenk, D. et al. Immunization with amyloid attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400, 173–177 (1999).

    CAS  PubMed  Google Scholar 

  62. DeMattos, R.B. et al. Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer's disease. Proc. Natl. Acad. Sci. USA 98, 8850–8855 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Janus, C. et al. Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease. Nature 408, 979–982 (2000).

    CAS  PubMed  Google Scholar 

  64. Morgan, D. et al. A β peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 408, 982–985 (2000).

    CAS  PubMed  Google Scholar 

  65. Ince, P.G. in Amyotrophic Lateral Sclerosis (eds. Brown, R. H. Jr., Meininger, V. & Swash, M.) 83–112 (Martin Dunitz, London, 2000).

    Google Scholar 

  66. Martin, L.J. Neuronal death in amyotrophic lateral sclerosis is apoptosis: possible contribution of a programmed cell death mechanism. J. Neuropathol. Exp. Neurol. 58, 459–471 (1999).

    CAS  PubMed  Google Scholar 

  67. Andersen, P.M., Morita, M. & Brown, R.H. Jr. in Amyotrophic Lateral Sclerosis (eds. Brown, R. H. Jr., Meininger, V. & Swash, M.) 223–250 (Martin Dunitz, London, 2000).

    Google Scholar 

  68. Cleveland, D.W. & Rothstein, J.D. From Charcot to Lou Gehrig: deciphering selective motor neurons death in ALS. Nature 2, 806–819 (2001).

    CAS  Google Scholar 

  69. Hadano, S. et al. A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. Nat. Genet. 29, 166–173 (2001).

    CAS  PubMed  Google Scholar 

  70. Yang, Y. et al. The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nat. Genet. 29, 160–165 (2001).

    CAS  PubMed  Google Scholar 

  71. Gurney, M.E. et al. Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science 264, 1772–1775 (1994).

    CAS  PubMed  Google Scholar 

  72. Wong, P.C. et al. An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron 14, 1105–1116 (1995).

    CAS  PubMed  Google Scholar 

  73. Bruijn, L.I. et al. ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron 18, 327–338 (1997).

    CAS  PubMed  Google Scholar 

  74. Jackson, M. & Rothstein, J.D. in Amyotrophic Lateral Sclerosis (eds. Brown, R. H. Jr., Meininger, V. & Swash, M.) 263–278 (Martin Dunitz, London, 2000).

    Google Scholar 

  75. Shaw, P.J. in Amyotrophic Lateral Sclerosis (eds. Brown, R. H. Jr., Meininger, V. & Swash, M.) 113–144 (Martin Dunitz, London, 2000).

    Google Scholar 

  76. Williamson, T.L. & Cleveland, D.W. Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons. Nat. Neurosci. 2, 50–56 (1999).

    CAS  PubMed  Google Scholar 

  77. Julien, J.-P. Amyotrophic lateral sclerosis: unfolding the toxicity of the misfolded. Cell 104, 581–591 (2001).

    CAS  PubMed  Google Scholar 

  78. Pasinelli, P., Borchelt, D.R., Houseweart, M.K., Cleveland, D.W. & Brown, R.H. Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosis-associated mutations in copper-zinc superoxide dismutase. Neurobiology 95, 15763–15768 (1998).

    CAS  Google Scholar 

  79. Couillard-Després, S. et al. Protective effect of neurofilament NF-H overexpression in motor neuron disease induced by mutant superoxide dismutase. Proc. Natl. Acad. Sci. USA 95, 9626–9630 (1998).

    PubMed  PubMed Central  Google Scholar 

  80. Klivenyi, P. et al. Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis. Nat. Med. 5, 347–350 (1999).

    CAS  PubMed  Google Scholar 

  81. Estévez, A.G. et al. Induction of nitric oxide-dependent apoptosis in motor neurons by zinc-deficient superoxide dismutase. Science 286, 2498–2500 (1999).

    PubMed  Google Scholar 

  82. Wong, P.C. et al. Copper chaperone for superoxide dismutase is essential to activate mammalian Cu/Zn superoxide dismutase. Proc. Natl. Acad. Sci. USA 97, 2886–2891 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Subramaniam, J.R. et al. Mutant SOD1 causes motor neuron disease independent of copper chaperone-mediated copper loading. Nat. Neurosci. 5, 301–307 (2002).

    CAS  PubMed  Google Scholar 

  84. Johnston, J.A., Dalton, M.J., Gurney, M.E. & Kopito, R.R. Formation of high molecular weight complexes of mutant Cu, Zn-superoxide dismutase in a mouse model for familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. USA 97, 12571–12576 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Bruijn, L.I. et al. Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1. Science 281, 1851–1854 (1998).

    CAS  PubMed  Google Scholar 

  86. Beaulieu, J.M., Jacomy, H. & Julien, J.P. Formation of intermediate filament protein aggregates with disparate effects in two transgenic mouse models lacking the neurofilament light subunit. J. Neurosci. 20, 5321–5328 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Eyer, J., Cleveland, D.W., Wong, P.C. & Peterson, A.C. Pathogenesis of two axonopathies does not require axonal neurofilaments. Nature 391, 584–587 (1998).

    CAS  PubMed  Google Scholar 

  88. Williamson, T.L. et al. Absence of neurofilaments reduces the selective vulnerability of motor neurons and slows disease caused by a familial amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutant. Proc. Natl. Acad. Sci. USA 95, 9631–9636 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Kong, J. & Xu, Z. Overexpression of neurofilament subunit NF-L and NF-H extends survival of a mouse model for amyotrophic lateral sclerosis. Neurosci. Lett. 281, 72–74 (2000).

    CAS  PubMed  Google Scholar 

  90. Crawford, T. & Pardo, C.A. The neurobiology of childhood spinal muscular atrophy. Neurobiol. Dis. 3, 97–110 (1996).

    CAS  PubMed  Google Scholar 

  91. Lefebvre, S. et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80, 155–165 (1995).

    CAS  PubMed  Google Scholar 

  92. Roy, N. et al. The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell 80, 167–178 (1995).

    CAS  PubMed  Google Scholar 

  93. Fischer, U., Liu, Q. & Dreyfuss, G. The SMN-SIP1 complex has an essential role in spliceosomal snRNP biogenesis. Cell 90, 1023–1029 (1997).

    CAS  PubMed  Google Scholar 

  94. Pagliardini, S. et al. Subcellular localization and axonal transport of the survival motor neuron (SMN) protein in the developing rat spinal cord. Hum. Mol. Genet. 9, 47–56 (2000).

    CAS  PubMed  Google Scholar 

  95. Jablonka, S., Schrank, B., Kralewski, M., Rossoll, W. & Sendtner, M. Reduced survival motor neuron (Smn) gene dose in mice leads to motor neuron degeneration: an animal model for spinal muscular atrophy type III. Hum. Mol. Genet. 9, 341–346 (2000).

    CAS  PubMed  Google Scholar 

  96. Hsieh-Li, H.M. et al. A mouse model for spinal muscular atrophy. Nat. Genet. 24, 66–70 (2000).

    CAS  PubMed  Google Scholar 

  97. Monani, U.R. et al. 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 (2000).

    CAS  PubMed  Google Scholar 

  98. Chang, J.-G. et al. Treatment of spinal muscular atrphy by sodium butyrate. Proc. Natl. Acad. Sci. USA 98, 9808–9813 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank colleagues from JHMI, particularly S. Sisodia, M. Lee, G. Thinakaren, E. Koo, J. Subramaniam, L. Martin, V. Koliatsos, A. Bergin, L. Brujin, C. Pardo, B. Rabin, T. Crawford, M. Becher, P. Hoffman, J. Griffin, J. Rothstein, J. Troncoso, T. Li, V. Culotta and D. Cleveland as well as those at other institutions (J. Gitlin) for contributions to the original work cited in this review and for discussions. Supported by grants from the U. S. Public Health Service (AG05146, AG07914, AG10480, AG10491, AG14248, NS07435, NS20471, NS37145, NS10580, NS37771, NS40014, NS38377, NS38065) as well as the Metropolitan Life Foundation, Adler Foundation, and Bristol-Myers Squibb Foundation.

Author information

Authors and Affiliations

  1. Department of Pathology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, 21205-2196, Maryland, USA

    Philip C. Wong, Huaibin Cai, David R. Borchelt & Donald L. Price

  2. Department of Neuroscience, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, 21205-2196, Maryland, USA

    Philip C. Wong, Huaibin Cai, David R. Borchelt & Donald L. Price

  3. Department of Neurology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, 21205-2196, Maryland, USA

    Donald L. Price

  4. The Division of Neuropathology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, 21205-2196, Maryland, USA

    Philip C. Wong, Huaibin Cai, David R. Borchelt & Donald L. Price

Authors
  1. Philip C. Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Huaibin Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David R. Borchelt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Donald L. Price
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Philip C. Wong.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wong, P., Cai, H., Borchelt, D. et al. Genetically engineered mouse models of neurodegenerative diseases. Nat Neurosci 5, 633–639 (2002). https://doi.org/10.1038/nn0702-633

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn0702-633

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing