Research advances in animal models of Wilson's disease

Yulong YANG; Taohua WEI; Wenming YANG; Wenjie HAO; Yue YANG; Nannan QIAN; Xiang LI; Hailin JIANG

doi:10.3969/j.issn.1001-5256.2022.05.041

Volume 38 Issue 5

May 2022

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Article Navigation > Journal of Clinical Hepatology > 2022 > 38(5): 1169-1174

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Research advances in animal models of Wilson's disease

DOI: 10.3969/j.issn.1001-5256.2022.05.041

1.
Graduate School of Anhui University of Chinese Medicine, Hefei 230000, China
2.
Encephalopathy Center, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230000, China
3.
Key Laboratory of Xin'an Medicine, Ministry of Education, Hefei 230000, China

Research funding:

National Natural Science Foundation of China (81973825);

National Project to Improve the Evidence-based Ability and Platform for TCM Encephalopathy (2019XZZX-NB001);

Open Foundation Project of Key Laboratory of Xin'an Medical Science, Ministry of Education, Anhui University of Chinese Medicine (2020xayx12);

The University Synergy Innovation Program of Anhui Province (GXXT-2020-025);

Anhui Provincial Natural Science Foundation Youth Funding Project (2108085QH367)

More Information

Corresponding author: YANG Wenming, yangwm8810@126.com(ORCID: 0000-0001-8268-9291)
Received Date: 2021-09-01
Published Date: 2022-05-20

Abstract

Abstract

Wilson's disease (WD) is a rare autosomal recessive disorder with a complex pathogenesis involving multiple systems, multiple visceral organs, and the complex copper homeostasis regulation system within the body. The liver is the most common organ for copper deposition, and liver injury is the earliest and most common manifestation of WD; therefore, it is important to find an ideal animal model for WD research. By summarizing the animal models of WD commonly used in the world, this article systematically summarizes the background, liver and nervous manifestations, and application of different models and compares the characteristics of different animal models, so as to provide a reference for the application of various animal models of WD.
- Hepatolenticular Degeneration,
- Liver Diseases,
- Disease Models, Animal

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References(45)

References

[1]	SUN ZR, YANG WM. Neurology[M]. Beijing: People's Medical Publishing House, 2016. 孙忠人, 杨文明. 神经病学[M]. 北京: 人民卫生出版社, 2016.
[2]	CZŁONKOWSKA A, LITWIN T, DUSEK P, et al. Wilson disease[J]. Nat Rev Dis Primers, 2018, 4(1): 21. DOI: 10.1038/s41572-018-0018-3.
[3]	XU CC, DONG JJ, CHENG N, et al. Effects of Gantou decoction serum on ATP7b protein subcellular localization and functional expression in Wilson disease model tx mice[J]. Chin J Tradit Chin Med Pharm, 2017, 32(1): 250-253. https://www.cnki.com.cn/Article/CJFDTOTAL-BXYY201701069.htm 徐陈陈, 董健健, 程楠, 等. 中药肝豆汤含药血清对Wilson病模型TX小鼠肝细胞内ATP7b蛋白亚细胞定位和功能表达的影响[J]. 中华中医药杂志, 2017, 32(1): 250-253. https://www.cnki.com.cn/Article/CJFDTOTAL-BXYY201701069.htm
[4]	ZHAO W, CHENG N, HAN YZ. Research progress of Wilson's disease animal model[J]. Anhui Med J, 2014, 35(11): 1611-1614. DOI: 10.3969/j.issn.1000-0399.2014.11.046. 赵雯, 程楠, 韩咏竹. Wilson病的动物模型研究进展[J]. 安徽医学, 2014, 35(11): 1611-1614. DOI: 10.3969/j.issn.1000-0399.2014.11.046.
[5]	REED E, LUTSENKO S, BANDMANN O. Animal models of Wilson disease[J]. J Neurochem, 2018, 146(4): 356-373. DOI: 10.1111/jnc.14323.
[6]	XIA M, SUN YH, WANG M, et al. Research progress of common animal models of primary hepatocellularcarcinoma[J]. J Clin Hepatol, 2021, 37(8): 1938-1942. DOI: 10.3969/j.issn.1001-5256.2021.08.042. 夏猛, 孙玉浩, 王萌, 等. 原发性肝癌常见动物模型的研究进展[J]. 临床肝胆病杂志, 2021, 37(8): 1938-1942. DOI: 10.3969/j.issn.1001-5256.2021.08.042.
[7]	RAUCH H. Toxic milk, a new mutation affecting cooper metabolism in the mouse[J]. J Hered, 1983, 74(3): 141-144. DOI: 10.1093/oxfordjournals.jhered.a109751.
[8]	CHEN X, WANG CH, FENG YQ, et al. Experimental study on copper metabolism and liver damage in TX mice[J]. Chin J Hepatol, 2009, 17(9): 688-690. DOI: 10.3760/cma.j.issn.1007-3418.2009.09.012. 陈曦, 王楚怀, 丰岩清, 等. TX小鼠铜代谢和肝损害的实验研究[J]. 中华肝脏病杂志, 2009, 17(9): 688-690. DOI: 10.3760/cma.j.issn.1007-3418.2009.09.012.
[9]	ZISCHKA H, LICHTMANNEGGER J. Pathological mitochondrial copper overload in livers of Wilson's disease patients and related animal models[J]. Ann N Y Acad Sci, 2014, 1315: 6-15. DOI: 10.1111/nyas.12347.
[10]	HOWELL JM, MERCER JF. The pathology and trace element status of the toxic milk mutant mouse[J]. J Comp Pathol, 1994, 110(1): 37-47. DOI: 10.1016/s0021-9975(08)80268-x.
[11]	ZHOU XX, LI XH, CHEN DB, et al. Injury factors and pathological features of toxic milk mice during different disease stages[J]. Brain Behav, 2019, 9(12): e01459. DOI: 10.1002/brb3.1459.
[12]	MEDICI V, HUSTER D. Animal models of Wilson disease[J]. Handb Clin Neurol, 2017, 142: 57-70. DOI: 10.1016/B978-0-444-63625-6.00006-9.
[13]	JIN S, FANG X, BAO YC, et al. Analysis on the characteristics of wilson's disease with renal damage as the main manifestation[J]. Clin J Tradit Chin Med, 2010, 22(11): 1005-1007. DOI: 10.16448/j.cjtcm.2010.11.032. 金珊, 方向, 鲍远程, 等. 以肾脏损害为主要发病表现的Wilson病特点分析[J]. 中医药临床杂志, 2010, 22(11): 1005-1007. DOI: 10.16448/j.cjtcm.2010.11.032.
[14]	ZHANG YH, LI M, QIN J, et al. Extra-nervous manifestations of hepatolenticular degeneration in children[J]. Clin J Appli Pediatr, 1999, 14(5): 277-278. DOI: 10.3969/j.issn.1003-515X.1999.05.024. 张月华, 李明, 秦炯, 等. 儿童肝豆状核变性的神经系统外表现[J]. 实用儿科临床杂志, 1999, 14(5): 277-278. DOI: 10.3969/j.issn.1003-515X.1999.05.024.
[15]	WU HM, CHEN DQ, ZHENG ZD. Hepatolenticular degeneration with renal damage as the first episode (report of 18 cases)[J]. Pediatr Emerg Med, 2001, 8(3): 175-191. DOI: 10.3760/cma.j.issn.1673-4912.2001.03.031. 吴红梅, 陈大庆, 郑祖德. 以肾脏损害首发的肝豆状核变性(附18例报告)[J]. 小儿急救医学, 2001, 8(3): 175-191. DOI: 10.3760/cma.j.issn.1673-4912.2001.03.031.
[16]	CHEN DB, FENG L, LIN XP, et al. Penicillamine increases free copper and enhances oxidative stress in the brain of toxic milk mice[J]. PLoS One, 2012, 7(5): e37709. DOI: 10.1371/journal.pone.0037709.
[17]	TANG LL, LIU DQ, LI R, et al. Protective effect and mechanism of Gandoufumu decoction on liver fibrosis in TX mice[J]. Chin J Integr Tradit West Med, 2018, 38(12): 1461-1466. DOI: 10.7661/j.cjim.20181023.312. 唐露露, 刘丹青, 李睿, 等. 肝豆扶木汤对TX小鼠肝纤维化的保护作用及机制研究[J]. 中国中西医结合杂志, 2018, 38(12): 1461-1466. DOI: 10.7661/j.cjim.20181023.312.
[18]	ZHANG J, TANG LL, LI LY, et al. Gandouling tablets inhibit excessive mitophagy in toxic milk (TX) model mouse of Wilson disease via Pink1/Parkin pathway[J]. Evid Based Complement Alternat Med, 2020, 2020: 3183714. DOI: 10.1155/2020/3183714.
[19]	BUCK NE, CHEAH DM, ELWOOD NJ, et al. Correction of copper metabolism is not sustained long term in Wilson's disease mice post bone marrow transplantation[J]. Hepatol Int, 2008, 2(1): 72-79. DOI: 10.1007/s12072-007-9039-9.
[20]	CORONADO V, NANJI M, COX DW. The Jackson toxic milk mouse as a model for copper loading[J]. Mamm Genome, 2001, 12(10): 793-795. DOI: 10.1007/s00335-001-3021-y.
[21]	JOŃCZY A, LIPIŃSKI P, OGÓREK M, et al. Functional iron deficiency in toxic milk mutant mice (TX-J) despite high hepatic ferroportin: A critical role of decreased GPI-ceruloplasmin expression in liver macrophages[J]. Metallomics, 2019, 11(6): 1079-1092. DOI: 10.1039/c9mt00035f.
[22]	TERWEL D, LÖSCHMANN YN, SCHMIDT HH, et al. Neuroinflammatory and behavioural changes in the Atp7B mutant mouse model of Wilson's disease[J]. J Neurochem, 2011, 118(1): 105-112. DOI: 10.1111/j.1471-4159.2011.07278.x.
[23]	PRZYBYŁKOWSKI A, GROMADZKA G, WAWER A, et al. Neurochemical and behavioral characteristics of toxic milk mice: an animal model of Wilson's disease[J]. Neurochem Res, 2013, 38(10): 2037-2045. DOI: 10.1007/s11064-013-1111-3.
[24]	MORDAUNT CE, SHIBATA NM, KIEFFER DA, et al. Epigenetic changes of the thioredoxin system in the TX-J mouse model and in patients with Wilson disease[J]. Hum Mol Genet, 2018, 27(22): 3854-3869. DOI: 10.1093/hmg/ddy262.
[25]	BOARU SG, MERLE U, UERLINGS R, et al. Simultaneous monitoring of cerebral metal accumulation in an experimental model of Wilson's disease by laser ablation inductively coupled plasma mass spectrometry[J]. BMC Neurosci, 2014, 15: 98. DOI: 10.1186/1471-2202-15-98.
[26]	ROYBAL JL, ENDO M, RADU A, et al. Early gestational gene transfer with targeted ATP7B expression in the liver improves phenotype in a murine model of Wilson's disease[J]. Gene Ther, 2012, 19(11): 1085-1094. DOI: 10.1038/gt.2011.186.
[27]	KLEIN D, LICHTANNEGGER J, FINCKH M, et al. Gene expression in the liver of Long-Evanscinnamon rats during the development of hepatitis[J]. Arch Toxicol, 2003, 77(10): 568-575. DOI: 10.1007/s00204-003-0493-4.
[28]	SAMUELE A, MANGIAGALLI A, ARMENTERO MT, et al. Oxidative stress and pro-apoptotic conditions in a rodent model of Wilson's disease[J]. Biochim Biophys Acta, 2005, 1741(3): 325-330. DOI: 10.1016/j.bbadis.2005.06.004.
[29]	STERNLIEB I, QUINTANA N, VOLENBERG I, et al. An array of mitochondrial alterations in the hepatocytes of Long-Evans Cinnamon rats[J]. Hepatology, 1995, 22(6): 1782-1787.
[30]	LEE BH, KIM JM, HEO SH, et al. Proteomic analysis of the hepatic tissue of Long-Evans Cinnamon (LEC) rats according to the natural course of Wilson disease[J]. Proteomics, 2011, 11(18): 3698-3705. DOI: 10.1002/pmic.201100122.
[31]	ZISCHKA H, LICHTMANNEGGER J, SCHMITT S, et al. Liver mitochondrial membrane crosslinking and destruction in a rat model of Wilson disease[J]. J Clin Invest, 2011, 121(4): 1508-1518. DOI: 10.1172/JCI45401.
[32]	LEVY E, BRUNET S, ALVAREZ F, et al. Abnormal hepatobiliary and circulating lipid metabolism in the Long-Evans Cinnamon rat model of Wilson's disease[J]. Life Sci, 2007, 80(16): 1472-1483. DOI: 10.1016/j.lfs.2007.01.017.
[33]	HAYASHI M, FUSE S, ENDOH D, et al. Accumulation of copper induces DNA strand breaks in brain cells of Long-Evans Cinnamon (LEC) rats, an animal model for human Wilson Disease[J]. Exp Anim, 2006, 55(5): 419-426. DOI: 10.1538/expanim.55.419.
[34]	TOGASHI Y, LI Y, KANG JH, et al. D-penicillamine prevents the development of hepatitis in Long-Evans Cinnamon rats[J]. Hepatology, 1992, 15(1): 82-87. DOI: 10.1002/hep.1840150116.
[35]	KLEIN D, ARORA U, LICHTMANNEGGER J, et al. Tetrathiomolybdate in the treatment of acute hepatitis in an animal model for Wilson disease[J]. J Hepatol, 2004, 40(3): 409-416. DOI: 10.1016/j.jhep.2003.11.034.
[36]	JABER FL, SHARMA Y, GUPTA S. Demonstrating potential of cell therapy for Wilson's disease with the long-evans cinnamon rat model[J]. Methods Mol Biol, 2017, 1506: 161-178. DOI: 10.1007/978-1-4939-6506-9_11.
[37]	CHEN S, SHAO C, DONG T, et al. Transplantation of ATP7B-transduced bone marrow mesenchymal stem cells decreases copper overload in rats[J]. PLoS One, 2014, 9(11): e111425. DOI: 10.1371/journal.pone.0111425.
[38]	AHMED S, DENG J, BORJIGIN J. A new strain of rat for functional analysis of PINA[J]. Brain Res Mol Brain Res, 2005, 137(1-2): 63-69. DOI: 10.1016/j.molbrainres.2005.02.025.
[39]	ZISCHKA H, LICHTMANNEGGER J, SCHMITT S, et al. Liver mitochondrial membrane crosslinking and destruction in a rat model of Wilson disease[J]. J Clin Invest, 2011, 121(4): 1508-1518. DOI: 10.1172/JCI45401.
[40]	LICHTMANNEGGER J, LEITZINGER C, WIMMER R, et al. Methanobactin reverses acute liver failure in a rat model of Wilson disease[J]. J Clin Invest, 2016, 126(7): 2721-2735. DOI: 10.1172/JCI85226.
[41]	FIETEN H, PENNING LC, LEEGWATER PA, et al. New canine models of copper toxicosis: diagnosis, treatment, and genetics[J]. Ann N Y Acad Sci, 2014, 1314: 42-48. DOI: 10.1111/nyas.12442.
[42]	HAYWOOD S, VAILLANT C. Overexpression of copper transporter CTR1 in the brain barrier of North Ronaldsay sheep: Implications for the study of neurodegenerative disease[J]. J Comp Pathol, 2014, 150(2-3): 216-224. DOI: 10.1016/j.jcpa.2013.09.002.
[43]	FIETEN H, GILL Y, MARTIN AJ, et al. The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: A new canine model for copper-metabolism disorders[J]. Dis Model Mech, 2016, 9(1): 25-38. DOI: 10.1242/dmm.020263.
[44]	HAYWOOD S, MVLLER T, MACKENZIE AM, et al. Copper-induced hepatotoxicosis with hepatic stellate cell activation and severe fibrosis in North Ronaldsay lambs: A model for non- Wilsonian hepatic copper toxicosis of infants[J]. J Comp Pathol, 2004, 130(4): 266-277. DOI: 10.1016/j.jcpa.2003.11.005.
[45]	BATALLER R, BRENNER DA. Hepatic stellate cells as a target for the treatment of liver fibrosis[J]. Semin Liver Dis, 2001, 21(3): 437-451. DOI: 10.1055/s-2001-17558.

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Research advances in animal models of Wilson's disease

DOI: 10.3969/j.issn.1001-5256.2022.05.041

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Research advances in animal models of Wilson's disease

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