A26 Transgenic miniature pig as an animal model for Huntington's disease

Baxa, M; Juhas, S; Pavlok, A; Vodicka, P; Juhasova, J; Hruška-Plocháň, M; Miyanohara, A; Marsala, M; Cattaneo, E; Difiglia, M; Motlik, J
September 2010
Journal of Neurology, Neurosurgery & Psychiatry;Sep2010 Supp, Vol. 81, pA8
Academic Journal
Huntington's disease (HD) is an inherited neurodegenerative disorder, characterised by psychiatric changes, cognitive disonance and motoric dysfunctions. The mutation responsible for this fatal disease is an abnormally expanded polyQ repeat within the gene encoding the huntingtin (htt) protein. Unfortunately, there is no specific cure available to stop disease progression. Numerous drugs have been developed to produce benefits in this disease, however, preclinical tests are required for confirmation of their effectiveness in treating HD. There are different animal models, each model with its own advantages and limitations, but there is still a huge demand for large animal models for testing the possibilities of HD therapies. As the extensive neuroanatomical and physiological studies indicate, a close similarity of the miniature pig brain to the human brain exists in term of neurochemical and neurotransmitter repertoire. Hence we chose this model for the generation of a transgenic model of HD. Lentiviral constructs encoding N terminal truncated (548aa) htt with 145 polyQ repeats under the control of human HD promoter were microinjected into the one cell stage embryos. The offspring born after embryo transfer were genotyped and one female piglet was transgenic. Both mutant htt incorporation into genome and its mRNA expression were proved using PCR. Western blot analysis confirmed the presence of the mutant htt protein. The transgenic gilt was mated with its brother to produce F1 generation. Three of eight newborn piglets are transgenic. The suitable and publicly acceptable large animal model of HD that can serve to validate the efficacy of treatment approaches targeted to modulate HD was generated. Mutant htt gene incorporated into porcine genome is not only transcribed into mRNA but is also expressed at the protein level. HD transgenic miniature gilt successfully conceived and delivered eight healthy offsprings. Three male piglets are transgenic in the litter.


Related Articles

  • Animal models.  // Journal of Neurology, Neurosurgery & Psychiatry;Sep2012 Supplement, Vol. 83, pA15 

    The article presents abstracts on animal models of Huntington's disease which includes catenin proteins expression in transgenic pigs, activation of cytokine production in animal models and expression of neuropathological features of disease characteristics in rats' model.

  • Pint-size pets. Wells, K. // Saturday Evening Post;Jul/Aug89, Vol. 261 Issue 5, p16 

    Discusses the current trend toward miniature animals, such as horses, rabbits, and pigs, as pets.

  • Melatonin Prolongs Life in Animal Model of Huntington's Disease. Dye, D. // Life Extension;Jan2012, Vol. 18 Issue 1, p19 

    The article discusses research which was published in the "Journal of Neuroscience" and found that melatonin prolongs life in an animal model of Huntington's disease.

  • Porcine Models of Accelerated Coronary Atherosclerosis: Role of Diabetes Mellitus and Hypercholesterolemia. Hamamdzic, Damir; Wilensky, Robert L. // Journal of Diabetes Research;2013, p1 

    Animal models of atherosclerosis have proven to be an invaluable asset in understanding the pathogenesis of the disease. However, large animal models may be needed in order to assess novel therapeutic approaches to the treatment of atherosclerosis. Porcine models of coronary and peripheral...

  • Targeted Disruption of LDLR Causes Hypercholesterolemia and Atherosclerosis in Yucatan Miniature Pigs. Davis, Bryan T.; Wang, Xiao-Jun; Rohret, Judy A.; Struzynski, Jason T.; Merricks, Elizabeth P.; Bellinger, Dwight A.; Rohret, Frank A.; Nichols, Timothy C.; Rogers, Christopher S. // PLoS ONE;Apr2014, Vol. 9 Issue 4, p1 

    Recent progress in engineering the genomes of large animals has spurred increased interest in developing better animal models for diseases where current options are inadequate. Here, we report the creation of Yucatan miniature pigs with targeted disruptions of the low-density lipoprotein...

  • A fly's eye view of Huntington's disease. Mitchell, Alison // Nature;10/29/1998, Vol. 395 Issue 6705, p841 

    Discusses research in the fruitfly Drosophila melanogaster regarding Huntington's disease. Mutations causing neurodegeneration; Value of the fruitfly animal model for the disease; Research by Jackson et al in `Neuron'; Cause of Huntington's disease; Effects of long glutamine tracts; Possibility...

  • Huntington's Disease.  // World Book Science Dataset;1/1/2009, p1 

    Huntington's Disease

  • Recent Trends in Detection of Huntingtin and Preclinical Models of Huntington's Disease. Mantha, Neelima; Das, Nandita G.; Das, Sudip K. // ISRN Otolaryngology;2014, p1 

    Huntington's disease is a genetically inherited neurodegenerative disease that is characterized by neuronal cell death in the brain. Molecular biology techniques to detect and quantify huntingtin protein in biological samples involve fluorescence imaging, western blotting, and PCR. Modified cell...

  • Neural transplantation in patients with Huntington's disease. Rosser, Anne E.; Dunnett, Stephen B. // CNS Drugs;2003, Vol. 17 Issue 12, p853 

    The gene for Huntington's disease was identified in 1993 as being a CAG repeat expansion in exon 1 of a gene now known as huntingtin on chromosome 4. Although many of the downstream effects of this mutant gene were identified in the subsequent years, a more detailed understanding of these events...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics