OMIA:000485-9823 : Huntington disease in Sus scrofa (pig)

In other species: crab-eating macaque , Rhesus monkey , sheep

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 143100 (trait) , 613004 (gene)

Links to relevant human diseases in MONDO:

Mendelian trait/disorder: yes

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2001

Species-specific description: Uchida et al. (2001) generated Huntington's disease (HD) pigs via prokaryotic injection. 
Yang et al. (2010) "generated transgenic Huntington's disease (HD) pigs that express N-terminal (208 amino acids) mutant huntingtin with an expanded polyglutamine tract (105Q). "Baxa et al. (2013) developed "HD transgenic (TgHD) minipigs encoding huntingtin (HTT)1-548 under the control of human HTT promoter". These animals are genetically-modified organisms (GMO). Yan et al. (2023) "show the feasibility of replacing expanded CAG repeats in the mutant HTT allele with a normal CAG repeat in genetically engineered pigs mimicking the selective neurodegeneration seen in patients with HD. A single intracranial or intravenous injection of adeno-associated virus encoding for Cas9, a single-guide RNA targeting the HTT gene, and donor DNA containing the normal CAG repeat led to the depletion of mutant HTT in the animals and to substantial reductions in the dysregulated expression and neurotoxicity of mutant HTT and in neurological symptoms."

History: Matsuyama et al. (2000) reported that the "Sus HD [Huntington Disease] gene closely resembles its human counterpart in terms of sequence and expression pattern. In particular, human-miniature pig similarities in the normal length of the CAG triplet repeat as well as its repeat-number polymorphism may indicate that miniature pig would provide a good animal model for Huntington's disease."

Genetic engineering: Yes - variants have been created artificially, e.g. by genetic engineering or gene editing
Have human generated variants been created, e.g. through genetic engineering and gene editing

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
HTT huntingtin Sus scrofa 8 NC_010450.4 (1809768..1934002) HTT Homologene, Ensembl , NCBI gene

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:000485-9823: Online Mendelian Inheritance in Animals (OMIA) [dataset].


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2024 Han, B., Liang, W., Li, X.J., Li, S., Yan, S., Tu, Z. :
Large animal models for Huntington's disease research. Zool Res 45:2095-8137(2024)02-0275-09:275-283, 2024. Pubmed reference: 38485497. DOI: 10.24272/j.issn.2095-8137.2023.199.
Handley, R.R., Reid, S.J., Burch, Z., Jacobsen, J.C., Gillis, T., Correia, K., Rudiger, S.R., McLaughlin, C.J., Bawden, C.S., MacDonald, M.E., Wheeler, V.C., Snell, R.G. :
Somatic CAG repeat stability in a transgenic sheep model of Huntington's disease. J Huntingtons Dis , 2024. Pubmed reference: 38393920. DOI: 10.3233/JHD-231516.
2023 Jia, Q., Bai, D., Zheng, X., Zhu, L., Ou, K., Wang, X., Tong, H., Zhang, Y., Wang, J., Zeng, J., Yan, S., Li, S., Li, X.J., Yin, P. :
Comparing HD knockin pigs and mice reveals the pathological role of IL-17. Cell Rep 42:113443, 2023. Pubmed reference: 37979175. DOI: 10.1016/j.celrep.2023.113443.
Tipatet, K., Du Boulay, I., Muir, H., Davison-Gates, L., Ellederová, Z., Downes, A. :
Raman spectroscopy of brain and skin tissue in a minipig model of Huntington's disease. Anal Methods , 2023. Pubmed reference: 38108410. DOI: 10.1039/d3ay00970j.
Tong, H., Yang, T., Liu, L., Li, C., Sun, Y., Jia, Q., Qin, Y., Chen, L., Zhao, X., Zhou, G., Yan, S., Li, X.J., Li, S. :
Aberrant splicing of mutant huntingtin in Huntington's disease knock-in pigs. Neurobiol Dis :106291, 2023. Pubmed reference: 37716514. DOI: 10.1016/j.nbd.2023.106291.
Upadhayay, S., Jamwal, S., Kumar, P. :
Animal models of Huntington's disease and their applicability to novel drug discovery and development. Expert Opin Drug Discov :1-12, 2023. Pubmed reference: 37042034. DOI: 10.1080/17460441.2023.2201493.
Yan, S., Zheng, X., Lin, Y., Li, C., Liu, Z., Li, J., Tu, Z., Zhao, Y., Huang, C., Chen, Y., Li, J., Song, X., Han, B., Wang, W., Liang, W., Lai, L., Li, X.J., Li, S. :
Cas9-mediated replacement of expanded CAG repeats in a pig model of Huntington's disease. Nat Biomed Eng 7:629-646, 2023. Pubmed reference: 36797418. DOI: 10.1038/s41551-023-01007-3.
2022 Lin, Y., Li, C., Wang, W., Li, J., Huang, C., Zheng, X., Liu, Z., Song, X., Chen, Y., Gao, J., Wu, J., Wu, J., Tu, Z., Lai, L., Li, X.J., Li, S., Yan, S. :
Intravenous AAV9 administration results in safe and widespread distribution of transgene in the brain of mini-pig. Front Cell Dev Biol 10:1115348, 2022. Pubmed reference: 36762127. DOI: 10.3389/fcell.2022.1115348.
2021 Bai, D., Yin, P., Zhang, Y., Sun, F., Chen, L., Lin, L., Yan, S., Li, S., Li, X.J. :
Lack of association of somatic CAG repeat expansion with striatal neurodegeneration in HD knock-in animal models. Hum Mol Genet 30:1497-1508, 2021. Pubmed reference: 33949657. DOI: 10.1093/hmg/ddab129.
Tanihara, F., Hirata, M., Otoi, T. :
Current status of the application of gene editing in pigs. J Reprod Dev 67:177-187, 2021. Pubmed reference: 33840678. DOI: 10.1262/jrd.2021-025.
Yang, W., Chen, X., Li, S., Li, X.J. :
Genetically modified large animal models for investigating neurodegenerative diseases. Cell Biosci 11:218, 2021. Pubmed reference: 34933675. DOI: 10.1186/s13578-021-00729-8.
2020 Howland, D., Ellederova, Z., Aronin, N., Fernau, D., Gallagher, J., Taylor, A., Hennebold, J., Weiss, A.R., Gray-Edwards, H., McBride, J. :
Large animal models of Huntington's disease: What we have learned and where we need to go next. J Huntingtons Dis 9:201-216, 2020. Pubmed reference: 32925082. DOI: 10.3233/JHD-200425.
2019 Smatlikova, P., Juhas, S., Juhasova, J., Suchy, T., Hubalek Kalbacova, M., Ellederova, Z., Motlik, J., Klima, J. :
Adipogenic differentiation of bone marrow-derived mesenchymal stem cells in pig transgenic model expressing human mutant Huntingtin. J Huntingtons Dis 8:33-51, 2019. Pubmed reference: 30584151. DOI: 10.3233/JHD-180303.
2018 Askeland, G., Rodinova, M., Štufková, H., Dosoudilova, Z., Baxa, M., Smatlikova, P., Bohuslavova, B., Klempir, J., Nguyen, T.D., Kuśnierczyk, A., Bjørås, M., Klungland, A., Hansikova, H., Ellederova, Z., Eide, L. :
A transgenic minipig model of Huntington's disease shows early signs of behavioral and molecular pathologies. Dis Model Mech 11, 2018. Pubmed reference: 30254085. DOI: 10.1242/dmm.035949.
Evers, M.M., Miniarikova, J., Juhas, S., Vallès, A., Bohuslavova, B., Juhasova, J., Skalnikova, H.K., Vodicka, P., Valekova, I., Brouwers, C., Blits, B., Lubelski, J., Kovarova, H., Ellederova, Z., van Deventer, S.J., Petry, H., Motlik, J., Konstantinova, P. :
AAV5-miHTT Gene Therapy Demonstrates Broad Distribution and Strong Human Mutant Huntingtin Lowering in a Huntington's Disease Minipig Model. Mol Ther 26:2163-2177, 2018. Pubmed reference: 30007561. DOI: 10.1016/j.ymthe.2018.06.021.
Liu, X., Peng, T., Li, H. :
Using Huntingtin Knock-In Minipigs to Fill the Gap Between Mouse Models and Patients with Huntington's Disease. Neurosci Bull 34:870-872, 2018. Pubmed reference: 30128692. DOI: 10.1007/s12264-018-0272-0.
Ratna, N., Jain, S. :
Huntington's disease pig model: Squealing into the spotlight. Mov Disord 33:1410-1411, 2018. Pubmed reference: 30311975. DOI: 10.1002/mds.96.
Reilmann, R., Schuldenzucker, V. :
Minipigs as a Large-Brained Animal Model for Huntington's Disease: From Behavior and Imaging to Gene Therapy. Methods Mol Biol 1780:241-266, 2018. Pubmed reference: 29856023. DOI: 10.1007/978-1-4939-7825-0_13.
Stower, H. :
A pig model of Huntington's disease. Nat Med 24:898, 2018. Pubmed reference: 29988131. DOI: 10.1038/s41591-018-0119-2.
Vidinská, D., Vochozková, P., Šmatlíková, P., Ardan, T., Klíma, J., Juhás, Š., Juhásová, J., Bohuslavová, B., Baxa, M., Valeková, I., Motlík, J., Ellederová, Z. :
Gradual Phenotype Development in Huntington Disease Transgenic Minipig Model at 24 Months of Age. Neurodegener Dis 18:107-119, 2018. Pubmed reference: 29870995. DOI: 10.1159/000488592.
Yan, S., Tu, Z., Liu, Z., Fan, N., Yang, H., Yang, S., Yang, W., Zhao, Y., Ouyang, Z., Lai, C., Yang, H., Li, L., Liu, Q., Shi, H., Xu, G., Zhao, H., Wei, H., Pei, Z., Li, S., Lai, L., Li, X.J. :
A Huntingtin knockin pig model recapitulates features of selective neurodegeneration in Huntington's disease. Cell 173:989-1002.e13, 2018. Pubmed reference: 29606351. DOI: 10.1016/j.cell.2018.03.005.
2017 Krizova, J., Stufkova, H., Rodinova, M., Macakova, M., Bohuslavova, B., Vidinska, D., Klima, J., Ellederova, Z., Pavlok, A., Howland, D.S., Zeman, J., Motlik, J., Hansikova, H. :
Mitochondrial Metabolism in a Large-Animal Model of Huntington Disease: The Hunt for Biomarkers in the Spermatozoa of Presymptomatic Minipigs. Neurodegener Dis 17:213-226, 2017. Pubmed reference: 28633139. DOI: 10.1159/000475467.
Schuldenzucker, V., Schubert, R., Muratori, L.M., Freisfeld, F., Rieke, L., Matheis, T., Schramke, S., Motlik, J., Kemper, N., Radespiel, U., Reilmann, R. :
Behavioral testing of minipigs transgenic for the Huntington gene-A three-year observational study. PLoS One 12:e0185970, 2017. Pubmed reference: 29016656. DOI: 10.1371/journal.pone.0185970.
2016 Holm, I.E., Alstrup, A.K., Luo, Y. :
Genetically modified pig models for neurodegenerative disorders. J Pathol 238:267-87, 2016. Pubmed reference: 26446984. DOI: 10.1002/path.4654.
Macakova, M., Bohuslavova, B., Vochozkova, P., Pavlok, A., Sedlackova, M., Vidinska, D., Vochyanova, K., Liskova, I., Valekova, I., Baxa, M., Ellederova, Z., Klima, J., Juhas, S., Juhasova, J., Klouckova, J., Haluzik, M., Klempir, J., Hansikova, H., Spacilova, J., Collins, R., Blumenthal, I., Talkowski, M., Gusella, J.F., Howland, D.S., DiFiglia, M., Motlik, J. :
Mutated Huntingtin Causes Testicular Pathology in Transgenic Minipig Boars. Neurodegener Dis 16:245-59, 2016. Pubmed reference: 26959244. DOI: 10.1159/000443665.
Schramke, S., Schuldenzucker, V., Schubert, R., Frank, F., Wirsig, M., Ott, S., Motlik, J., Fels, M., Kemper, N., Hölzner, E., Reilmann, R. :
Behavioral phenotyping of minipigs transgenic for the Huntington gene. J Neurosci Methods 265:34-45, 2016. Pubmed reference: 26688470. DOI: 10.1016/j.jneumeth.2015.11.013.
2015 Chang, R., Liu, X., Li, S., Li, X.J. :
Transgenic animal models for study of the pathogenesis of Huntington's disease and therapy. Drug Des Devel Ther 9:2179-88, 2015. Pubmed reference: 25931812. DOI: 10.2147/DDDT.S58470.
Li, X.J., Li, S. :
Large Animal Models of Huntington's Disease. Curr Top Behav Neurosci 22:149-60, 2015. Pubmed reference: 24048953. DOI: 10.1007/7854_2013_246.
2013 Baxa, M., Hruska-Plochan, M., Juhas, S., Vodicka, P., Pavlok, A., Juhasova, J., Miyanohara, A., Nejime, T., Klima, J., Macakova, M., Marsala, S., Weiss, A., Kubickova, S., Musilova, P., Vrtel, R., Sontag, E.M., Thompson, L.M., Schier, J., Hansikova, H., Howland, D.S., Cattaneo, E., DiFiglia, M., Marsala, M., Motlik, J. :
A transgenic minipig model of Huntington's Disease. J Huntingtons Dis 2:47-68, 2013. Pubmed reference: 25063429. DOI: 10.3233/JHD-130001.
2010 Yang, D., Wang, C.E., Zhao, B., Li, W., Ouyang, Z., Liu, Z., Yang, H., Fan, P., O'Neill, A., Gu, W., Yi, H., Li, S., Lai, L., Li, X.J. :
Expression of Huntington's disease protein results in apoptotic neurons in the brains of cloned transgenic pigs. Hum Mol Genet 19:3983-94, 2010. Pubmed reference: 20660116. DOI: 10.1093/hmg/ddq313.
2001 Uchida, M., Shimatsu, Y., Onoe, K., Matsuyama, N., Niki, R., Ikeda, J.E., Imai, H. :
Production of transgenic miniature pigs by pronuclear microinjection. Transgenic Res 10:577-82, 2001. Pubmed reference: 11817545. DOI: 10.1023/a:1013059917280.
2000 Matsuyama, N., Hadano, S., Onoe, K., Osuga, H., Showguchi-Miyata, J., Gondo, Y., Ikeda, J.E. :
Identification and characterization of the miniature pig Huntington's disease gene homolog: Evidence for conservation and polymorphism in the CAG triplet repeat Genomics 69:72-85, 2000. Pubmed reference: 11013077. DOI: 10.1006/geno.2000.6317.

Edit History

  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Frank Nicholas on 30 Sep 2019
  • Changed by Imke Tammen2 on 26 May 2021
  • Changed by Imke Tammen2 on 25 Jun 2021
  • Changed by Imke Tammen2 on 26 Dec 2021
  • Changed by Imke Tammen2 on 09 Jan 2022
  • Changed by Imke Tammen2 on 15 Feb 2023
  • Changed by Imke Tammen2 on 18 Feb 2023
  • Changed by Imke Tammen2 on 10 Dec 2023
  • Changed by Imke Tammen2 on 08 Apr 2024