Genetically Modified Pig Models for Human Diseases

Nana Fan; Liangxue Lai

doi:10.1016/j.jgg.2012.07.014

Volume 40 Issue 2

Feb. 2013

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Genetically Modified Pig Models for Human Diseases

doi: 10.1016/j.jgg.2012.07.014

Nana Fan^{a, b},
Liangxue Lai^a

a
Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
b
School of Life Sciences, University of Science and Technology of China, Hefei 230027, China

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Corresponding author: E-mail address: Lai_liangxue@gibh.ac.cn (Liangxue Lai)
Received Date: 2012-05-29
Accepted Date: 2012-12-30
Rev Recd Date: 2012-12-10

Available Online: 2013-01-08

Publish Date: 2013-02-20

Abstract

Abstract

Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies. Although genetically modified mice have been widely used to model human diseases, some of these mouse models do not replicate important disease symptoms or pathology. Pigs are more similar to humans than mice in anatomy, physiology, and genome. Thus, pigs are considered to be better animal models to mimic some human diseases. This review describes genetically modified pigs that have been used to model various diseases including neurological, cardiovascular, and diabetic disorders. We also discuss the development in gene modification technology that can facilitate the generation of transgenic pig models for human diseases.
- Pig,
- Transgene,
- Gene targeting,
- Human disease model

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References(60)

References

[1]	Alberg, A.J., Lam, A.P., Helzlsouer, K.J. Epidemiology, prevention, and early detection of breast cancer Curr. Opin. Oncol., 11 (1999),pp. 435-441
[2]	Baggio, L.L., Drucker, D.J. Biology of incretins: GLP-1 and GIP Gastroenterology, 132 (2007),pp. 2131-2157
[3]	Bendixen, E., Danielsen, M., Larsen, K. et al. Advances in porcine genomics and proteomics – a toolbox for developing the pig as a model organism for molecular biomedical research Brief Funct. Genomics, 9 (2010),pp. 208-219
[4]	Berson, E.L. Retinitis pigmentosa. The Friedenwald Lecture Invest. Ophthalmol. Vis. Sci., 34 (1993),pp. 1659-1676
[5]	Bertram, L., Lill, C.M., Tanzi, R.E. The genetics of Alzheimer disease: back to the future Neuron, 68 (2010),pp. 270-281
[6]	Chang, B., Hawes, N.L., Hurd, R.E. et al. Retinal degeneration mutants in the mouse Vision Res., 42 (2002),pp. 517-525
[7]	Edwards, A.O., Miedziak, A., Vrabec, T. et al. Autosomal dominant Stargardt-like macular dystrophy: I. Clinical characterization, longitudinal follow-up, and evidence for a common ancestry in families linked to chromosome 6q14 Am. J. Ophthalmol., 127 (1999),pp. 426-435
[8]	Gargini, C., Terzibasi, E., Mazzoni, F. et al. J. Comp. Neurol., 500 (2007),pp. 222-238
[9]	Gowen, L.C., Johnson, B.L., Latour, A.M. et al. Brca1 deficiency results in early embryonic lethality characterized by neuroepithelial abnormalities Nat. Genet., 12 (1996),pp. 191-194
[10]	Hagenfeldt-Johansson, K.A., Herrera, P.L., Wang, H. et al. Beta-cell-targeted expression of a dominant-negative hepatocyte nuclear factor-1 alpha induces a maturity-onset diabetes of the young (MODY)3-like phenotype in transgenic mice Endocrinology, 142 (2001),pp. 5311-5320
[11]	Hakem, R., de la Pompa, J.L., Sirard, C. et al. Cell, 85 (1996),pp. 1009-1023
[12]	Hao, Y.H., Yong, H.Y., Murphy, C.N. et al. Production of endothelial nitric oxide synthase (eNOS) over-expressing piglets Transgenic Res., 15 (2006),pp. 739-750
[13]	Herbach, N., Goeke, B., Schneider, M. et al. Overexpression of a dominant negative GIP receptor in transgenic mice results in disturbed postnatal pancreatic islet and beta-cell development Regul. Pept., 125 (2005),pp. 103-117
[14]	Iwasaki, N., Ogata, M., Tomonaga, O. et al. Liver and kidney function in Japanese patients with maturity-onset diabetes of the young Diabetes Care, 21 (1998),pp. 2144-2148
[15]	Jones, B.W., Marc, R.E. Retinal remodeling during retinal degeneration Exp. Eye Res., 81 (2005),pp. 123-137
[16]	Kragh, P.M., Nielsen, A.L., Li, J. et al. Transgenic Res., 18 (2009),pp. 545-558
[17]	Lai, L., Prather, R.S. Creating genetically modified pigs by using nuclear transfer Reprod. Biol. Endocrinol., 1 (2003),p. 82
[18]	Le, T.T., Pham, L.T., Butchbach, M.E. et al. Hum. Mol. Genet., 14 (2005),pp. 845-857
[19]	Li, X.J., Li, W. Beyond mice: genetically modifying larger animals to model human diseases J. Genet. Genomics, 39 (2012),pp. 237-238
[20]	Liedtke, A.J., Hughes, H.C., Neely, J.R. An experimental model for studying myocardial ischemia. Correlation of hemodynamic performance and metabolism in the working swine heart J. Thorac. Cardiovasc. Surg., 69 (1975),pp. 203-211
[21]	Lind, N.M., Moustgaard, A., Jelsing, J. et al. The use of pigs in neuroscience: modeling brain disorders Neurosci. Biobehav. Rev., 31 (2007),pp. 728-751
[22]	Lorson, M.A., Spate, L.D., Samuel, M.S. et al. Transgenic Res., 20 (2011),pp. 1293-1304
[23]	Luo, Y., Li, J., Liu, Y. et al. Transgenic Res., 20 (2011),pp. 975-988
[24]	McKenzie, J.E., Scandling, D.M., Ahle, N.W. et al. Effects of soman (pinacolyl methylphosphonofluoridate) on coronary blood flow and cardiac function in swine Fundam. Appl. Toxicol., 29 (1996),pp. 140-146
[25]	Michaud, M., Arnoux, T., Bielli, S. et al. Neuromuscular defects and breathing disorders in a new mouse model of spinal muscular atrophy Neurobiol. Dis., 38 (2010),pp. 125-135
[26]	Miyawaki, K., Yamada, Y., Yano, H. et al. Glucose intolerance caused by a defect in the entero-insular axis: a study in gastric inhibitory polypeptide receptor knockout mice Proc. Natl. Acad. Sci. USA, 96 (1999),pp. 14843-14847
[27]	Monani, U.R., Pastore, M.T., Gavrilina, T.O. et al. J. Cell Biol., 160 (2003),pp. 41-52
[28]	Muir, E.R., De La Garza, B., Duong, T.Q. Blood flow and anatomical MRI in a mouse model of retinitis pigmentosa Magn. Reson. Med. (2012)
[29]	Nissen, S.E., Wolski, K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes N. Engl. J. Med, 356 (2007),pp. 2457-2471
[30]	Okouchi, M., Ekshyyan, O., Maracine, M. et al. Neuronal apoptosis in neurodegeneration Antioxid. Redox. Signal., 9 (2007),pp. 1059-1096
[31]	Petters, R.M., Alexander, C.A., Wells, K.D. et al. Genetically engineered large animal model for studying cone photoreceptor survival and degeneration in retinitis pigmentosa Nat. Biotechnol., 15 (1997),pp. 965-970
[32]	Prior, T.W. Spinal muscular atrophy: a time for screening Curr. Opin. Pediatr., 22 (2010),pp. 696-702
[33]	Pruhova, S., Ek, J., Lebl, J. et al. Diabetologia, 46 (2003),pp. 291-295
[34]	Raslova, K. An update on the treatment of type 1 and type 2 diabetes mellitus: focus on insulin detemir, a long-acting human insulin analog Vasc. Health Risk Manag., 6 (2010),pp. 399-410
[35]	Reiner, A., Dragatsis, I., Dietrich, P. Genetics and neuropathology of Huntington's disease Int. Rev. Neurobiol., 98 (2011),pp. 325-372
[36]	Renner, S., Fehlings, C., Herbach, N. et al. Glucose intolerance and reduced proliferation of pancreatic beta-cells in transgenic pigs with impaired glucose-dependent insulinotropic polypeptide function Diabetes, 59 (2010),pp. 1228-1238
[37]	Rosen, E.M., Fan, S., Pestell, R.G. et al. J. Cell Physiol., 196 (2003),pp. 19-41
[38]	Ross, J.W., Fernandez de Castro, J.P., Zhao, J. et al. Generation of an inbred miniature pig model of retinitis pigmentosa Invest. Ophthalmol. Vis. Sci., 53 (2012),pp. 501-507
[39]	Sears, E.H., Gartman, E.J., Casserly, B.P. Treatment options for cystic fibrosis: state of the art and future perspectives Rev. Recent Clin. Trials, 6 (2011),pp. 94-107
[40]	Sommer, J.R., Estrada, J.L., Collins, E.B. et al. Br. J. Ophthalmol., 95 (2011),pp. 1749-1754
[41]	Stoltz, D.A., Meyerholz, D.K., Pezzulo, A.A. et al. Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth Sci. Transl. Med., 2 (2010),pp. 29-31
[42]	Takeuchi, A., Irizarry, M.C., Duff, K. et al. Age-related amyloid beta deposition in transgenic mice overexpressing both Alzheimer mutant presenilin 1 and amyloid beta precursor protein Swedish mutant is not associated with global neuronal loss Am. J. Pathol., 157 (2000),pp. 331-339
[43]	Thomas, H., Badenberg, B., Bulman, M. et al. Biol. Chem., 383 (2002),pp. 1691-1700
[44]	Uchida, M., Shimatsu, Y., Onoe, K. et al. Production of transgenic miniature pigs by pronuclear microinjection Transgenic Res., 10 (2001),pp. 577-582
[45]	Umeyama, K., Watanabe, M., Saito, H. et al. Dominant-negative mutant hepatocyte nuclear factor 1alpha induces diabetes in transgenic-cloned pigs Transgenic Res., 18 (2009),pp. 697-706
[46]	Verma, N., Rettenmeier, A.W., Schmitz-Spanke, S. Proteomics, 11 (2011),pp. 776-793
[47]	Walsh, D.M., Klyubin, I., Shankar, G.M. et al. The role of cell-derived oligomers of Abeta in Alzheimer's disease and avenues for therapeutic intervention Biochem. Soc. Trans., 33 (2005),pp. 1087-1090
[48]	Walters, E.M., Agca, Y., Ganjam, V. et al. Animal models got you puzzled?: think pig Ann. N. Y. Acad. Sci., 1245 (2011),pp. 63-64
[49]	Watanabe, M., Umeyama, K., Kawano, H.O. et al. The production of a diabetic mouse using constructs encoding porcine insulin promoter-driven mutant human hepatocyte nuclear factor-1alpha J. Reprod. Dev., 53 (2007),pp. 189-200
[50]	Wei, J., Ouyang, H., Wang, Y. et al. Characterization of a hypertriglyceridemic transgenic miniature pig model expressing human apolipoprotein CIII FEBS J., 279 (2012),pp. 91-99
[51]	Welsh, M.J., Rogers, C.S., Stoltz, D.A. et al. Development of a porcine model of cystic fibrosis Trans. Am. Clin. Climatol. Assoc., 120 (2009),pp. 149-162
[52]	Whyte, J., Laughlin, M.H. Placentation in the pig visualized by eGFP fluorescence in eNOS over-expressing cloned transgenic swine Mol. Reprod. Dev., 77 (2010),p. 565
[53]	Whyte, J.J., Samuel, M., Mahan, E. et al. Vascular endothelium-specific overexpression of human catalase in cloned pigs Transgenic Res., 20 (2011),pp. 989-1001
[54]	Whyte, J.J., Prather, R.S. J. Anim. Sci., 90 (2012),pp. 1111-1117
[55]	Wilke, M., Buijs-Offerman, R.M., Aarbiou, J. et al. Mouse models of cystic fibrosis: phenotypic analysis and research applications J. Cyst. Fibros, 10 (2011),pp. S152-S171
[56]	Yao, Z., Wang, Y. Apolipoprotein C-III and hepatic triglyceride-rich lipoprotein production Curr. Opin. Lipidol., 23 (2012),pp. 206-212
[57]	Yang, D., Wang, C.E., Zhao, B. et al. Expression of Huntington's disease protein results in apoptotic neurons in the brains of cloned transgenic pigs Hum. Mol. Genet., 19 (2010),pp. 3983-3994
[58]	Yang, D., Yang, H., Li, W. et al. Cell Res., 21 (2011),pp. 979-982
[59]	Zanoteli, E., Maximino, J.R., Conti Reed, U. et al. Spinal muscular atrophy: from animal model to clinical trial Funct. Neurol., 25 (2010),pp. 73-79
[60]	Zaragoza, C., Gomez-Guerrero, C., Martin-Ventura, J.L. et al. Animal models of cardiovascular diseases J. Biomed. Biotechnol., 2011 (2011),p. 497841