An Update on the Use of Animal Models in Diabetic Nephropathy Research
详细信息    查看全文
  • 作者：Boris Betz ; Bryan R. Conway
  • 关键词：Diabetic nephropathy ; Animal models ; Hypertension ; Transcriptomics ; Regression
  • 刊名：Current Diabetes Reports
  • 出版年：2016
  • 出版时间：February 2016
  • 年：2016
  • 卷：16
  • 期：2
  • 全文大小：1,063 KB
  • 参考文献：1.Saran R, Li Y, Robinson B, Ayanian J, Balkrishnan R, Bragg-Gresham J, et al. US renal data system 2014 annual data report: epidemiology of kidney disease in the united states. Am J Kidney Dis. 2015;65(6 Suppl 1):A7.CrossRef
    2.Finne P, Reunanen A, Stenman S, Groop PH, Gronhagen-Riska C. Incidence of end-stage renal disease in patients with type 1 diabetes. JAMA. 2005;294(14):1782–7.CrossRef PubMed
    3.Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. New Eng J Med. 2012;367(23):2204–13.CrossRef PubMed
    4.de Zeeuw D, Akizawa T, Audhya P, Bakris GL, Chin M, Christ-Schmidt H, et al. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. New Eng J Med. 2013;369(26):2492–503.CrossRef PubMedCentral PubMed
    5.Fried LF, Emanuele N, Zhang JH, Brophy M, Conner TA, Duckworth W, et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. New Eng J Med. 2013;369(20):1892–903.CrossRef PubMed
    6.Fernandez-Fernandez B, Ortiz A, Gomez-Guerrero C, Egido J. Therapeutic approaches to diabetic nephropathy—beyond the RAS. Nat Rev Nephrol. 2014;10(6):325–46.CrossRef PubMed
    7.Brosius 3rd FC, Alpers CE, Bottinger EP, Breyer MD, Coffman TM, Gurley SB, et al. Mouse models of diabetic nephropathy. J Am Soc Nephrol. 2009;20(12):2503–12.CrossRef PubMedCentral PubMed
    8.Brosius 3rd FC, Alpers CE. New targets for treatment of diabetic nephropathy: what we have learned from animal models. Curr Opin Nephrol Hypertens. 2013;22(1):17–25.PubMedCentral PubMed
    9.Breyer MD, Bottinger E, Brosius 3rd FC, Coffman TM, Harris RC, Heilig CW, et al. Mouse models of diabetic nephropathy. J Am Soc Nephrol. 2005;16(1):27–45.CrossRef PubMed
    10.Wang J, Takeuchi T, Tanaka S, Kubo SK, Kayo T, Lu D, et al. A mutation in the insulin 2 gene induces diabetes with severe pancreatic beta-cell dysfunction in the Mody mouse. J Clin Invest. 1999;103(1):27–37.CrossRef PubMedCentral PubMed
    11.Epstein PN, Overbeek PA, Means AR. Calmodulin-induced early-onset diabetes in transgenic mice. Cell. 1989;58(6):1067–73.CrossRef PubMed
    12.Chua Jr SC, Chung WK, Wu-Peng XS, Zhang Y, Liu SM, Tartaglia L, et al. Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor. Science. 1996;271(5251):994–6.CrossRef PubMed
    13.Chen H, Charlat O, Tartaglia LA, Woolf EA, Weng X, Ellis SJ, et al. Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell. 1996;84(3):491–5.CrossRef PubMed
    14.Zucker LM, Antoniades HN. Insulin and obesity in the Zucker genetically obese rat "fatty". Endocrinology. 1972;90(5):1320–30.CrossRef PubMed
    15.Mallipattu SK, Gallagher EJ, LeRoith D, Liu R, Mehrotra A, Horne SJ, et al. Diabetic nephropathy in a nonobese mouse model of type 2 diabetes mellitus. Am J Physiol. 2014;306(9):F1008–17.
    16.Freedman BI, Bostrom M, Daeihagh P, Bowden DW. Genetic factors in diabetic nephropathy. Clin J Am Soc Nephrology : CJASN. 2007;2(6):1306–16.CrossRef
    17.Sandholm N, Salem RM, McKnight AJ, Brennan EP, Forsblom C, Isakova T, et al. New susceptibility loci associated with kidney disease in type 1 diabetes. PLoS Genet. 2012;8(9):e1002921.CrossRef PubMedCentral PubMed
    18.•
Qi Z, Fujita H, Jin J, Davis LS, Wang Y, Fogo AB, et al. Characterization of susceptibility of inbred mouse strains to diabetic nephropathy. Diabetes. 2005;54(9):2628–37. This very useful paper describes the physiological and pathological features observed when diabetes is induced in several common strains of mice. CrossRef PubMed
19.Chua Jr S, Li Y, Liu SM, Liu R, Chan KT, Martino J, et al. A susceptibility gene for kidney disease in an obese mouse model of type II diabetes maps to chromosome 8. Kidney Int. 2010;78(5):453–62.CrossRef PubMedCentral PubMed
20.Yuzawa Y, Niki I, Kosugi T, Maruyama S, Yoshida F, Takeda M, et al. Overexpression of calmodulin in pancreatic beta cells induces diabetic nephropathy. J Am Soc Nephrol. 2008;19(9):1701–11.CrossRef PubMedCentral PubMed
21.••
Hudkins KL, Pichaiwong W, Wietecha T, Kowalewska J, Banas MC, Spencer MW, et al. BTBR Ob/Ob mutant mice model progressive diabetic nephropathy. J Am Soc Nephrol. 2010;21(9):1533–42. This paper describes for the first time the use of leptin deficient on the BTBR strain of mouse to model many of the features of human DN. CrossRef PubMedCentral PubMed
22.Gilbert RE, Cooper ME. The tubulointerstitium in progressive diabetic kidney disease: more than an aftermath of glomerular injury? Kidney Int. 1999;56(5):1627–37.CrossRef PubMed
23.Aitman TJ, Critser JK, Cuppen E, Dominiczak A, Fernandez-Suarez XM, Flint J, et al. Progress and prospects in rat genetics: a community view. Nat Genet. 2008;40(5):516–22.CrossRef PubMed
24.Yagihashi S, Goto Y, Kakizaki M, Kaseda N. Thickening of glomerular basement membrane in spontaneously diabetic rats. Diabetologia. 1978;15(4):309–12.CrossRef PubMed
25.Kawano K, Hirashima T, Mori S, Natori T. OLETF (Otsuka Long-Evans Tokushima Fatty) rat: a new NIDDM rat strain. Diabetes Res Clin Pract. 1994;24(Suppl):S317–20.CrossRef PubMed
26.Geurts AM, Cost GJ, Freyvert Y, Zeitler B, Miller JC, Choi VM, et al. Knockout rats via embryo microinjection of zinc-finger nucleases. Science. 2009;325(5939):433.CrossRef PubMedCentral PubMed
27.Kern TS, Engerman RL. Arrest of glomerulopathy in diabetic dogs by improved glycaemic control. Diabetologia. 1990;33(9):522–5.CrossRef PubMed
28.Steffes MW, Buchwald H, Wigness BD, Groppoli TJ, Rupp WM, Rohde TD, et al. Diabetic nephropathy in the uninephrectomized dog: microscopic lesions after one year. Kidney Int. 1982;21(5):721–4.CrossRef PubMed
29.Maile LA, Busby WH, Gollahon KA, Flowers W, Garbacik N, Garbacik S, et al. Blocking ligand occupancy of the alphaVbeta3 integrin inhibits the development of nephropathy in diabetic pigs. Endocrinology. 2014;155(12):4665–75.CrossRef PubMedCentral PubMed
30.Intine RV, Olsen AS, Sarras Jr MP. A zebrafish model of diabetes mellitus and metabolic memory. J Vis Exp : JoVE. 2013;72:e50232.PubMed
31.Olsen AS, Sarras Jr MP, Leontovich A, Intine RV. Heritable transmission of diabetic metabolic memory in zebrafish correlates with DNA hypomethylation and aberrant gene expression. Diabetes. 2012;61(2):485–91.CrossRef PubMedCentral PubMed
32.••
Weavers H, Prieto-Sanchez S, Grawe F, Garcia-Lopez A, Artero R, Wilsch-Brauninger M, et al. The insect nephrocyte is a podocyte-like cell with a filtration slit diaphragm. Nature. 2009;457(7227):322–6. This paper demonstrates that specialised cells in Drosophila called nephrocytes exhibit features similar to human podocytes including slit diaphragms, and inhibition of signalling pathways known to be important in human podocytes results in disrupts the nephrocyte slit diaphragm. The tractability of Drosophila to genetic modification affords a opportunity to study podocyte signalling very efficiently.CrossRef PubMedCentral PubMed
33.Zhang F, Zhao Y, Chao Y, Muir K, Han Z. Cubilin and amnionless mediate protein reabsorption in Drosophila nephrocytes. J Am Soc Nephrol. 2013;24(2):209–16.CrossRef PubMedCentral PubMed
34.Na J, Sweetwyne MT, Park AS, Susztak K, Cagan RL. Diet-Induced Podocyte Dysfunction in Drosophila and Mammals. Cell Report. 2015;12(4):636–47.CrossRef
35.Cooper ME. Pathogenesis, prevention, and treatment of diabetic nephropathy. Lancet. 1998;352(9123):213–9.CrossRef PubMed
36.Mogensen CE. Combined high blood pressure and glucose in type 2 diabetes: double jeopardy. British trial shows clear effects of treatment, especially blood pressure reduction. Brit Med J. 1998;317(7160):693–4.CrossRef PubMedCentral PubMed
37.Lurbe E, Redon J, Kesani A, Pascual JM, Tacons J, Alvarez V, et al. Increase in nocturnal blood pressure and progression to microalbuminuria in type 1 diabetes. New Eng J Med. 2002;347(11):797–805.CrossRef PubMed
38.Roglic G, Colhoun HM, Stevens LK, Lemkes HH, Manes C, Fuller JH. Parental history of hypertension and parental history of diabetes and microvascular complications in insulin-dependent diabetes mellitus: the EURODIAB IDDM Complications Study. Diabet Med. 1998;15(5):418–26.CrossRef PubMed
39.Berkman J, Rifkin H. Unilateral nodular diabetic glomerulosclerosis (Kimmelstiel-Wilson): report of a case. Metab Clin Exp. 1973;22(5):715–22.CrossRef PubMed
40.Beroniade VC, Lefebvre R, Falardeau P. Unilateral nodular diabetic glomerulosclerosis: recurrence of an experiment of nature. Am J Nephrol. 1987;7(1):55–9.CrossRef PubMed
41.Zatz R, Meyer TW, Rennke HG, Brenner BM. Predominance of hemodynamic rather than metabolic factors in the pathogenesis of diabetic glomerulopathy. Proc Natl Acad Sci U S A. 1985;82(17):5963–7.CrossRef PubMedCentral PubMed
42.Zatz R, Dunn BR, Meyer TW, Anderson S, Rennke HG, Brenner BM. Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest. 1986;77(6):1925–30.CrossRef PubMedCentral PubMed
43.Zheng S, Huang Y, Yang L, Chen T, Xu J, Epstein PN. Uninephrectomy of diabetic OVE26 mice greatly accelerates albuminuria, fibrosis, inflammatory cell infiltration and changes in gene expression. Nephron Exp Nephrol. 2011;119(1):e21–32.CrossRef PubMedCentral PubMed
44.Cooper ME, Allen TJ, Macmillan P, Bach L, Jerums G, Doyle AE. Genetic hypertension accelerates nephropathy in the streptozotocin diabetic rat. Am J Hypertens. 1988;1(1):5–10.PubMed
45.Kelly DJ, Wilkinson-Berka JL, Allen TJ, Cooper ME, Skinner SL. A new model of diabetic nephropathy with progressive renal impairment in the transgenic (mRen-2)27 rat (TGR). Kidney Int. 1998;54(2):343–52.CrossRef PubMed
46.Janssen U, Riley SG, Vassiliadou A, Floege J, Phillips AO. Hypertension superimposed on type II diabetes in Goto Kakizaki rats induces progressive nephropathy. Kidney Int. 2003;63(6):2162–70.CrossRef PubMed
47.•
Conway BR, Rennie J, Bailey MA, Dunbar DR, Manning JR, Bellamy CO, et al. Hyperglycemia and renin-dependent hypertension synergize to model diabetic nephropathy. J Am Soc Nephrol. 2012;23(3):405–11. This study determined that streptozotocin-induced hyperglycaemia alone was insufficient to promote significant nephropathy, but when combined with renin-dependent hypertension there was progressive nephropathy which resembled many of the histological features and transcriptomic changes observed in human diabetic kidney disease. CrossRef PubMedCentral PubMed
48.Thibodeau JF, Holterman CE, Burger D, Read NC, Reudelhuber TL, Kennedy CR. A novel mouse model of advanced diabetic kidney disease. PLoS One. 2014;9(12), e113459.CrossRef PubMedCentral PubMed
49.Hartner A, Cordasic N, Klanke B, Wittmann M, Veelken R, Hilgers KF. Renal injury in streptozotocin-diabetic Ren2-transgenic rats is mainly dependent on hypertension, not on diabetes. Am J Physiol. 2007;292(2):F820–7.
50.Nakagawa T, Johnson RJ. Endothelial nitric oxide synthase. Contrib Nephrol. 2011;170:93–101.CrossRef PubMed
51.Nakayama T, Sato W, Kosugi T, Zhang L, Campbell-Thompson M, Yoshimura A, et al. Endothelial injury due to eNOS deficiency accelerates the progression of chronic renal disease in the mouse. Am J Physiol. 2008.
52.Nakagawa T, Sato W, Glushakova O, Heinig M, Clarke T, Campbell-Thompson M, et al. Diabetic endothelial nitric oxide synthase knockout mice develop advanced diabetic nephropathy. J Am Soc Nephrol. 2007;18(2):539–50.CrossRef PubMed
53.Zhao HJ, Wang S, Cheng H, Zhang MZ, Takahashi T, Fogo AB, et al. Endothelial nitric oxide synthase deficiency produces accelerated nephropathy in diabetic mice. J Am Soc Nephrol. 2006;17(10):2664–9.CrossRef PubMedCentral PubMed
54.Jenkins AJ, Lyons TJ, Zheng D, Otvos JD, Lackland DT, McGee D, et al. Lipoproteins in the DCCT/EDIC cohort: associations with diabetic nephropathy. Kidney Int. 2003;64(3):817–28.CrossRef PubMed
55.Plump AS, Smith JD, Hayek T, Aalto-Setala K, Walsh A, Verstuyft JG, et al. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell. 1992;71(2):343–53.CrossRef PubMed
56.Lassila M, Seah KK, Allen TJ, Thallas V, Thomas MC, Candido R, et al. Accelerated nephropathy in diabetic apolipoprotein e-knockout mouse: role of advanced glycation end products. J Am Soc Nephrol. 2004;15(8):2125–38.CrossRef PubMed
57.Yamamoto Y, Kato I, Doi T, Yonekura H, Ohashi S, Takeuchi M, et al. Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice. J Clin Invest. 2001;108(2):261–8.CrossRef PubMedCentral PubMed
58.Lindenmeyer MT, Kretzler M, Boucherot A, Berra S, Yasuda Y, Henger A, et al. Interstitial vascular rarefaction and reduced VEGF-A expression in human diabetic nephropathy. J Am Soc Nephrol. 2007;18(6):1765–76.CrossRef PubMed
59.Merchant ML, Perkins BA, Boratyn GM, Ficociello LH, Wilkey DW, Barati MT, et al. Urinary peptidome may predict renal function decline in type 1 diabetes and microalbuminuria. J Am Soc Nephrol. 2009;20(9):2065–74.CrossRef PubMedCentral PubMed
60.Rossing K, Mischak H, Dakna M, Zurbig P, Novak J, Julian BA, et al. Urinary proteomics in diabetes and CKD. J Am Soc Nephrol. 2008;19(7):1283–90.CrossRef PubMedCentral PubMed
61.••Hodgin JB, Nair V, Zhang H, Randolph A, Harris RC, Nelson RG, et al. Identification of cross-species shared transcriptional networks of diabetic nephropathy in human and mouse glomeruli. Diabetes. 2013;62(1):299–308. This study employed transcriptomic data to determine that when compared with other models diabetic eNOS−/− mice more closely replicated the molecular pathways activated in the glomeruli in human diabetic kidney disease. CrossRef PubMedCentral PubMed
62.Siwy J, Zoja C, Klein J, Benigni A, Mullen W, Mayer B, et al. Evaluation of the Zucker diabetic fatty (ZDF) rat as a model for human disease based on urinary peptidomic profiles. PLoS One. 2012;7(12):e51334.CrossRef PubMedCentral PubMed
63.Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS. Regression of microalbuminuria in type 1 diabetes. N Engl J Med. 2003;348(23):2285–93.CrossRef PubMed
64.Fioretto P, Steffes MW, Sutherland DER, Goetz FC, Mauer M. reversal of lesions of diabetic nephropathy after pancreas transplantations. New Eng J Med. 1998;339:69–75.CrossRef PubMed
65.Fioretto P, Sutherland DE, Najafian B, Mauer M. Remodeling of renal interstitial and tubular lesions in pancreas transplant recipients. Kidney Int. 2006;69(5):907–12.CrossRef PubMed
66.••Pichaiwong W, Hudkins KL, Wietecha T, Nguyen TQ, Tachaudomdach C, Li W, et al. Reversibility of structural and functional damage in a model of advanced diabetic nephropathy. J Am Soc Nephrol. 2013;24(7):1088–102. Administration of leptin to BTBR ob/ob mice reduced obesity and hyperglycaemia and this model may be used to investigate the mechanisms that promote regression of fibrosis in the human diabetic kidne. CrossRef PubMedCentral PubMed
67.Conway BR, Betz B, Sheldrake TA, Manning JR, Dunbar DR, Dobyns A, et al. Tight blood glycaemic and blood pressure control in experimental diabetic nephropathy reduces extracellular matrix production without regression of fibrosis. Nephrol Carlton Vic. 2014;19(12):802–13.CrossRef
  • 作者单位：Boris Betz (1) (3)
    Bryan R. Conway (2)

    1. Centre for Inflammation Research, University of Edinburgh, Edinburgh, Scotland
    3. Department of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Jena, Germany
    2. Centre for Cardiovascular Science, Queen’s Medical Research Centre, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland
  • 刊物主题：Diabetes;
  • 出版者：Springer US
  • ISSN：1539-0829
    • 文摘
    In the current review, we discuss limitations and recent advances in animal models of diabetic nephropathy (DN). As in human disease, genetic factors may determine disease severity with the murine FVB and DBA/2J strains being more susceptible to DN than C57BL/6J mice. On the black and tan, brachyuric (BTBR) background, leptin deficient (ob/ob) mice develop many of the pathological features of human DN. Hypertension synergises with hyperglycemia to promote nephropathy in rodents. Moderately hypertensive endothelial nitric oxide synthase (eNOS−/−) deficient diabetic mice develop hyaline arteriosclerosis and nodular glomerulosclerosis and induction of renin-dependent hypertension in diabetic Cyp1a1mRen2 rats mimics moderately severe human DN. In addition, diabetic eNOS−/− mice and Cyp1a1mRen2 rats recapitulate many of the molecular pathways activated in the human diabetic kidney. However, no model exhibits all the features of human DN; therefore, researchers should consider biochemical, pathological, and transcriptomic data in selecting the most appropriate model to study their molecules and pathways of interest. Keywords Diabetic nephropathy Animal models Hypertension Transcriptomics Regression

    © 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

    地址：北京市海淀区学院路29号 邮编：100083

    电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700