Towards a transgenic model of Huntington’s disease in a non-human primate (original) (raw)

References

1. Cummings, C. J. & Zoghbi, H. Y. Trinucleotide repeats: mechanisms and pathophysiology. Annu. Rev. Genomics Hum. Genet. 1, 281–328 (2000)
   Article CAS Google Scholar
2. Davies, S. & Ramsden, D. B. Huntington's disease. Mol. Pathol. 54, 409–413 (2001)
   Article CAS Google Scholar
3. Myers, R. H., Marans, K. S. & MacDonald, M. E. Huntington’s Disease in Genetic Instabilities and Hereditary Neurological Diseases (eds Wells, R. D. & Warren, S. T.) 301–324 (Academic, San Diego, 1998)
   Google Scholar
4. Rubinsztein, D. C. Lessons from animal models of Hungtington's disease. Trends Genet. 18, 202–209 (2002)
   Article CAS Google Scholar
5. MacDonald, M. E. et al. HD research collaborative groups. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntintgton’s disease chromosome. Cell 72, 971–983 (1993)
   Article Google Scholar
6. Sharp, A. H. et al. Widespread expression of Huntington’s disease gene (IT15) protein product. Neuron 14, 1065–1074 (1995)
   Article CAS Google Scholar
7. Lane, M. A. Nonhuman primate models in biogerontology. Exp. Gerontol. 35, 533–541 (2000)
   Article CAS Google Scholar
8. King, M. C. & Wilson, A. C. Evolution at two levels in humans and chimpanzees. Science 188, 107–116 (1975)
   Article ADS CAS Google Scholar
9. McConkey, E. H. & Varki, A. A primate genome project deserves high priority. Science 289, 1295–1296 (2000)
   Article CAS Google Scholar
10. Chan, A. W. S., Chong, K. Y., Martinovich, C., Simerly, C. & Schatten, G. Transgenic monkeys produced by retroviral gene transfer into mature oocytes. Science 291, 309–312 (2001)
    Article ADS CAS Google Scholar
11. Chan, A. W. S., Chong, K. Y. & Schatten, G. in Transgenic Animal Technology: A Laboratory Handbook (ed. Pinkert, C. A.) (Academic, San Diego, 2002)
    Google Scholar
12. Zhou, H. et al. Huntingtin forms toxic NH2-terminal fragment complexes that are promoted by the age-dependent decrease in proteasome activity. J. Cell Biol. 163, 109–118 (2003)
    Article CAS Google Scholar
13. Gutekunst, C. A. et al. Nuclear and neuropil aggregates in Huntington’s disease: relationship to neuropathology. J. Neurosci. 19, 2522–2534 (1999)
    Article CAS Google Scholar
14. Bates, G. P., Mangiarini, L., Wanker, E. E. & Davies, S. W. Polyglutamine expansion and Huntington’s disease. Biochem. Soc. Trans. 26, 471–475 (1998)
    Article CAS Google Scholar
15. Lin, C. H. et al. Neurological abnormalities in a knock-in mouse model of Huntington’s disease. Hum. Mol. Genet. 10, 137–144 (2001)
    Article CAS Google Scholar
16. Li, H. et al. Ultrastructural localization and progressive formation of neuropil aggregates in Huntington’s disease transgenic mice. Hum. Mol. Genet. 8, 1227–1236 (1999)
    Article CAS Google Scholar
17. Li, H., Li, S. H., Yu, Z. X., Shelbourne, P. & Li, X. J. Huntingtin aggregate-associated axonal degeneration is an early pathological event in Huntington’s disease mice. J. Neurosci. 21, 8473–8481 (2001)
    Article CAS Google Scholar
18. Yu, Z. X. et al. Mutant Huntingtin causes context-dependent neurodegeneration in mice with Huntington’s disease. J. Neurosci. 23, 2193–2202 (2003)
    Article CAS Google Scholar
19. Davies, S. W. et al. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90, 537–548 (1997)
    Article CAS Google Scholar
20. DiFiglia, M. et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neuritis in brain. Science 277, 1990–1993 (1997)
    Article CAS Google Scholar
21. Yang, S. H. et al. Enhanced transgenesis by intracytoplasmic injection of envelope-free lentivirus. Genesis 45, 177–183 (2007)
    Article CAS Google Scholar

Download references

Acknowledgements

We thank J. Fanton (deceased), M. Zelinski-Wooten, M. Sparman and D. Wolf for consultation, C. Lois for lentivirus backbone and C. Testa for critical review of the manuscript. We also thank F. Zhang, T. Caspary, S. Warren, J. Greene, T. Wichmann, M. Wilson, S. Chikazawa, K. Gould, L. Walker, K. Layug, E. Strobert, J. Else, J. Ksiazek, K. Strait, F. Stroud, J. Jenkins, J. Cohen, J. Pare, S. Jenkins, K. Paul, S. Lackey, J. Johnson-Ward, the veterinary staff, the animal resource and the endocrine core laboratory at the Yerkes National Primate Research Center. Acryline was provided by NICHD/NIH. All transgenic HD monkeys were housed under the guideline of the IACUC approved procedures and the support of YNPRC Division of Animal Resources. All newborn monkeys were closely monitored by the veterinary staff and infant care personnel. All procedures were approved by YNPRC/Emory Animal Care and Biosafety Committees. The YNPRC is supported by NIH/NCRR. A.W.S.C., S.H.L. and X.J.-L are supported by grants awarded by the NIH.

Author Contributions S.-H.Y. carried out assisted reproductive technique (ART) in monkeys, viral gene transfer, construct design and molecular analysis; P.-H.C., construct design and evaluation; K.P.-N., ART in monkeys; H.B., animal management; behavioural testing and all animal procedures; K.L., animal care and behavioural testing; E.C.H.C., molecular analysis; J.-J.Y., preparation of high titre lentiviruses; B.S., J.L. and Z.H.F., neuropathological analysis; J.O., surgical procedures and animal care; Y.S., neuropathological analysis; J.B., design of behavioural and cognitive testing; S.M.Z., experimental design and manuscript preparation; S.H.L. and X.J.-L., construct design, analysis and manuscript preparation; A.W.S.C., ART in monkey, viral gene transfer, experimental design, construct design, molecular analysis and manuscript preparation.

Author information

Author notes

1. Shang-Hsun Yang, Pei-Hsun Cheng and Heather Banta: These authors contributed equally to this work.

Authors and Affiliations

1. Yerkes National Primate Research Center,,
   Shang-Hsun Yang, Pei-Hsun Cheng, Heather Banta, Karolina Piotrowska-Nitsche, Jin-Jing Yang, Eric C. H. Cheng, Brooke Snyder, Katherine Larkin, Jun Liu, Jack Orkin, Yoland Smith, Jocelyne Bachevalier, Stuart M. Zola & Anthony W. S. Chan
2. Department of Human Genetics,,
   Shang-Hsun Yang, Pei-Hsun Cheng, Karolina Piotrowska-Nitsche, Jin-Jing Yang, Eric C. H. Cheng, Brooke Snyder, Jun Liu, Zhi-Hui Fang, Shi-Hua Li, Xiao-Jiang Li & Anthony W. S. Chan
3. Genetics and Molecular Biology Program,,
   Shang-Hsun Yang, Xiao-Jiang Li & Anthony W. S. Chan
4. Neuroscience Program,,
   Jun Liu, Yoland Smith, Stuart M. Zola, Xiao-Jiang Li & Anthony W. S. Chan
5. Department of Neurology,,
   Yoland Smith
6. Department of Psychology,,
   Jocelyne Bachevalier
7. Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia 30329, USA,
   Jocelyne Bachevalier & Stuart M. Zola
8. Department of Experimental Embryology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, 05-552 Wolka-Kosowska, Poland
   Karolina Piotrowska-Nitsche
9. Veterans Affairs Medical Center, Atlanta, Georgia 30033, USA ,
   Stuart M. Zola

Authors

1. Shang-Hsun Yang
   You can also search for this author inPubMed Google Scholar
2. Pei-Hsun Cheng
   You can also search for this author inPubMed Google Scholar
3. Heather Banta
   You can also search for this author inPubMed Google Scholar
4. Karolina Piotrowska-Nitsche
   You can also search for this author inPubMed Google Scholar
5. Jin-Jing Yang
   You can also search for this author inPubMed Google Scholar
6. Eric C. H. Cheng
   You can also search for this author inPubMed Google Scholar
7. Brooke Snyder
   You can also search for this author inPubMed Google Scholar
8. Katherine Larkin
   You can also search for this author inPubMed Google Scholar
9. Jun Liu
   You can also search for this author inPubMed Google Scholar
10. Jack Orkin
    You can also search for this author inPubMed Google Scholar
11. Zhi-Hui Fang
    You can also search for this author inPubMed Google Scholar
12. Yoland Smith
    You can also search for this author inPubMed Google Scholar
13. Jocelyne Bachevalier
    You can also search for this author inPubMed Google Scholar
14. Stuart M. Zola
    You can also search for this author inPubMed Google Scholar
15. Shi-Hua Li
    You can also search for this author inPubMed Google Scholar
16. Xiao-Jiang Li
    You can also search for this author inPubMed Google Scholar
17. Anthony W. S. Chan
    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toAnthony W. S. Chan.

Supplementary information

Rights and permissions

About this article

Cite this article

Yang, SH., Cheng, PH., Banta, H. et al. Towards a transgenic model of Huntington’s disease in a non-human primate.Nature 453, 921–924 (2008). https://doi.org/10.1038/nature06975

Download citation

• Received: 07 January 2008
• Accepted: 09 April 2008
• Published: 18 May 2008
• Issue Date: 12 June 2008
• DOI: https://doi.org/10.1038/nature06975