title: Generation of c-Myc transgenic pigs for autosomal dominant polycystic kidney disease.
abstract: After several decades of research, autosomal dominant polycystic kidney disease (ADPKD) is still incurable and imposes enormous physical, psychological, and economic burdens on patients and their families. Murine models of ADPKD represent invaluable tools for studying this disease. These murine forms of ADPKD can arise spontaneously, or they can be induced via chemical or genetic manipulations. Although these models have improved our understanding of the etiology and pathogenesis of ADPKD, they have not led to effective treatment strategies. The mini-pig represents an effective biomedical model for studying human diseases, as the pig's human-like physiological processes help to understand disease mechanisms and to develop novel therapies. Here, we tried to generate a transgenic model of ADPKD in pigs by overexpressing c-Myc in kidney tissue. Western-blot analysis showed that c-Myc was overexpressed in the kidney, brain, heart, and liver of transgenic pigs. Immunohistochemical staining of kidney tissue showed that exogenous c-Myc predominantly localized to renal tubules. Slightly elevated blood urea nitrogen levels were observed in transgenic pigs 1 month after birth, but no obvious abnormalities were detected after that time. In the future, we plan to subject this model to renal injury in an effort to promote ADPKD progression.
authors.affiliation: State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing, 100193, China, yjh6scxh@cau.edu.cn.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Ye
authors.forename: Jin
authors.initials: J
authors.lastname: He
authors.forename: Qiuyan
authors.initials: Q
authors.lastname: Li
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Feng
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Bai
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Chen
authors.forename: Yaofeng
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Hu
authors.forename: Zhengquan
authors.initials: Z
authors.lastname: Yu
authors.forename: Ning
authors.initials: N
authors.lastname: Li
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000378:metabolism; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D013552:Swine; D013556:Swine, Miniature
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc
references.citation: J Am Soc Nephrol. 2010 Jul;21(7):1073-6
references.pmid: 20488953
references.citation: Sci China C Life Sci. 2006 Apr;49(2):164-71
references.pmid: 16704120
references.citation: Mol Cell Biol. 1990 Mar;10(3):1192-8
references.pmid: 2304463
references.citation: Nephrol Dial Transplant. 2008 Apr;23(4):1157-65
references.pmid: 18048422
references.citation: J Am Soc Nephrol. 2011 May;22(5):793-5
references.pmid: 21493772
references.citation: Cell Metab. 2012 Feb 8;15(2):157-70
references.pmid: 22326218
references.citation: Oncogene. 1996 Sep 19;13(6):1153-60
references.pmid: 8808689
references.citation: J Am Soc Nephrol. 2009 Nov;20(11):2389-402
references.pmid: 19833899
references.citation: Am J Physiol. 1999 Oct;277(4):F599-610
references.pmid: 10516285
references.citation: Dis Mon. 1995 Nov;41(11):693-765
references.pmid: 7587886
references.citation: Nat Biotechnol. 2010 May;28(5):436-40
references.pmid: 20458311
references.citation: Lancet. 2007 Apr 14;369(9569):1287-1301
references.pmid: 17434405
references.citation: J Am Soc Nephrol. 1995 Jan;5(7):1462-8
references.pmid: 7703384
references.citation: Cancer Cell. 2012 Feb 14;21(2):155-67
references.pmid: 22340590
references.citation: Transplantation. 1998 Jun 27;65(12):1584-90
references.pmid: 9665074
references.citation: Nat Rev Cancer. 2008 Dec;8(12):976-90
references.pmid: 19029958
references.citation: J Reprod Dev. 2009 Apr;55(2):99-104
references.pmid: 19008650
references.citation: Cell. 1996 Dec 13;87(6):979-87
references.pmid: 8978603
references.citation: CSH Protoc. 2006 Jun 01;2006(1):
references.pmid: 22485678
references.citation: J Am Soc Nephrol. 1999 Jul;10(7):1524-9
references.pmid: 10405208
references.citation: Am J Pathol. 1998 Jan;152(1):219-29
references.pmid: 9422539
references.citation: J Clin Invest. 1997 Jan 15;99(2):194-9
references.pmid: 9005987
references.citation: Cold Spring Harb Protoc. 2010 May;2010(5):pdb.prot5434
references.pmid: 20439421
references.citation: Nat Med. 2007 Dec;13(12):1490-5
references.pmid: 17965720
references.citation: J Am Soc Nephrol. 1991 Feb;1(8):1048-53
references.pmid: 1912403
references.citation: Kidney Int. 1999 Apr;55(4):1187-97
references.pmid: 10200981
references.citation: Arterioscler Thromb Vasc Biol. 2007 Oct;27(10):2177-83
references.pmid: 17656674
references.citation: N Engl J Med. 2004 Jan 8;350(2):151-64
references.pmid: 14711914
references.citation: J Biol Chem. 2008 Nov 14;283(46):31559-66
references.pmid: 18782757
references.citation: Hum Mol Genet. 2009 Jul 15;18(14):2532-42
references.pmid: 19401297
references.citation: N Engl J Med. 1993 Jul 29;329(5):332-42
references.pmid: 8321262
references.citation: Cancer Cell. 2008 Dec 9;14(6):447-57
references.pmid: 19061836
references.citation: Kidney Int. 1991 Apr;39(4):665-71
references.pmid: 1646908
references.citation: Nat Med. 2003 Jan;9(1):53-60
references.pmid: 12496960
references.citation: Am J Physiol. 1999 Oct;277(4):F587-98
references.pmid: 10516284
references.citation: J Am Soc Nephrol. 2002 Jul;13(7):1824-36
references.pmid: 12089378
references.citation: PLoS Genet. 2012;8(3):e1002573
references.pmid: 22438825
references.citation: Circ Res. 2001 Dec 7;89(12):1122-9
references.pmid: 11739276
references.citation: Hum Mol Genet. 2000 Nov 1;9(18):2617-27
references.pmid: 11063721
references.citation: N Engl J Med. 2008 Oct 2;359(14):1477-85
references.pmid: 18832246
references.citation: Gene. 2011 Dec 15;490(1-2):37-46
references.pmid: 21945688
references.citation: J Am Soc Nephrol. 2008 Dec;19(12):2351-63
references.pmid: 18776127
references.citation: Anim Genet. 1999 Jun;30(3):204-6
references.pmid: 10442983
references.citation: Hum Mol Genet. 2009 Jul 15;18(14):2523-31
references.pmid: 19342421
references.citation: Transgenic Res. 2012 Apr;21(2):407-14
references.pmid: 21805108
references.citation: Mamm Genome. 1994 Mar;5(3):149-52
references.pmid: 8199402
references.citation: Mol Cell Biochem. 1991 May 29-Jun 12;104(1-2):15-9
references.pmid: 1921994
references.citation: Proc Natl Acad Sci U S A. 1987 Dec;84(23):8394-8
references.pmid: 3479800
references.citation: Hum Mol Genet. 1999 Mar;8(3):509-13
references.pmid: 9949210
references.citation: Hum Mol Genet. 2010 Apr 1;19(7):1174-89
references.pmid: 20053665
references.citation: Curr Opin Genet Dev. 2010 Feb;20(1):91-5
references.pmid: 19962879
references.citation: Hum Mol Genet. 2004 Dec 15;13(24):3069-77
references.pmid: 15496422
references.citation: N Engl J Med. 2010 Aug 26;363(9):820-9
references.pmid: 20581391
references.citation: Hum Mol Genet. 2007 Dec 15;16(24):3188-96
references.pmid: 17932118
references.citation: Space Life Sci. 1972 Jun;3(3):226-34
references.pmid: 4556756
references.citation: N Engl J Med. 2010 Aug 26;363(9):830-40
references.pmid: 20581392
references.citation: J Am Soc Nephrol. 2011 May;22(5):839-48
references.pmid: 21493775
references.citation: J Clin Invest. 2012 Nov;122(11):4257-73
references.pmid: 23064367
references.citation: Mol Cell. 1998 Aug;2(2):247-51
references.pmid: 9734362
references.citation: Nat Med. 2010 Jan;16(1):106-10
references.pmid: 19966811
references.citation: J Mol Cell Cardiol. 1997 Jul;29(7):1895-902
references.pmid: 9236143
references.citation: Meat Sci. 2004 Nov;68(3):431-8
references.pmid: 22062411