Animal models are essential tools to understand the mechanisms underlying the development and progression of renal disease and to study potential therapeutic approaches. Recently, interventional models suitable to induce acute and chronic kidney disease in the mouse have become a focus of interest due to the wide availability of genetically engineered mouse lines. These models differ by their damaging mechanism (cell toxicity, immune mechanisms, surgical renal mass reduction, ischemia, hypertension, ureter obstruction etc.), functional and histomorphological phenotype and disease evolution. The susceptibility to a damaging mechanism often depends on strain and gender. The C57BL/6 strain, the most commonly used genetic background of transgenic mice, appears to be relatively resistant against developing glomerulosclerosis, proteinuria and hypertension. This review serves to provide a comprehensive overview of interventional mouse models of acute and chronic kidney disease.

Keywords:
Fibrosis, Mouse, Kidney disease, Mouse models
1.
Hewitson TD, Ono T, Becker GJ: Small animal models of kidney disease: a review; in Hewitson TD, Becker GJ (eds): Kidney Research. Methods in Molecular Biology. Totowa NJ, Humana Press, 2009, vol 466.
2.
Ma LJ, Fogo AB: Model of robust induction of glomerulosclerosis in mice: importance of genetic background. Kidney Int 2003;64:350-355.
3.
Qi Z, Fujita H, Jin J, Davis LS, Wang Y, Fogo AB, Breyer MD: Characterization of susceptibility of inbred mouse strains to diabetic nephropathy. Diabetes 2005;54:2628-2637.
4.
Ishola DA Jr, van der Giezen DM, Hahnel B, Goldschmeding R, Kriz W, Koomans HA, Joles JA: In mice, proteinuria and renal inflammatory responses to albumin overload are strain-dependent. Nephrol Dial Transplant 2006;21:591-597.
5.
Hartner A, Cordasic N, Klanke B, Veelken R, Hilgers KF: Strain differences in the development of hypertension and glomerular lesions induced by deoxycorticosterone acetate salt in mice. Nephrol Dial Transplant 2003;18:1999-2004.
6.
Wang Q, Hummler E, Nussberger J, Clément S, Gabbiani G, Brunner HR, Burnier M: Blood pressure, cardiac, and renal responses to salt and deoxycorticosterone acetate in mice: role of renin genes. J Am Soc Nephrol 2002;13:1509-1516.
7.
Hu H, Wang G, Batteux F, Nicco C: Gender differences in the susceptibility to renal ischemia-reperfusion injury in BALB/c mice. Tohoku J Exp Med 2009;218:325-329.
8.
Gurley SB, Clare SE, Snow KP, Hu A, Meyer TW, Coffman TM: Impact of genetic background on nephropathy in diabetic mice. Am J Physiol Renal Physiol 2006;290:F214-F222.
9.
Eddy AA, Lopez-Guisa JM, Okamura DM, Yamaguchi I: Investigating mechanisms of chronic kidney disease in mouse models. Pediatr Nephrol 2012;27:1233-1247.
10.
Sánchez-González PD, López-Hernández FJ, López-Novoa JM, Morales AI: An integrative view of the pathophysiological events leading to cisplatin nephrotoxicity. Crit Rev Toxicol 2011;41:803-821.
11.
Chen CL, Liao JW, Hu OY, Pao LH: Blockade of KCa3.1 potassium channels protects against cisplatin-induced acute kidney injury. Arch Toxicol 2015, Epub ahead of print.
12.
Torres R, Velazquez H, Chang JJ, Levene MJ, Moeckel G, Desir GV, Safirstein R: Three-dimensional morphology by multiphoton microscopy with clearing in a model of cisplatin-induced CKD. J Am Soc Nephrol 2016;27:1102-1112.
13.
Dickman KG, Sweet DH, Bonala R, Ray T, Wu A: Physiological and molecular characterization of aristolochic acid transport by the kidney. J Pharmacol Exp Ther 2011;338:588-597.
14.
Huang L, Scarpellini A, Funck M, Verderio EA, Johnson TS: Development of a chronic kidney disease model in C57BL/6 mice with relevance to human pathology. Nephron Extra 2013;3:12-29.
15.
Zhou Y, Bian X, Fang L, He W, Dai C, Yang J: Aristolochic acid causes albuminuria by promoting mitochondrial DNA damage and dysfunction in podocyte. PLoS One 2013;8:e83408.
16.
Wang Y, Wang YP, Tay YC, Harris DC: Progressive adriamycin nephropathy in mice: sequence of histologic and immunohistochemical events. Kidney Int 2000;58:1797-1804.
17.
Papeta N, Zheng Z, Schon EA, Brosel S, Altintas MM, Nasr SH, Reiser J, D'Agati VD, Gharavi AG: PRKDC participates in mitochondrial genome maintenance and prevents adriamycin-induced nephropathy in mice. J Clin Invest 2010;120:4055-4064.
18.
Stallons LJ, Whitaker RM, Schnellmann RG: Suppressed mitochondrial biogenesis in folic acid-induced acute kidney injury and early fibrosis. Toxicol Lett 2014;224:326-332.
19.
Fink M, Henry M, Tange JD: Experimental folic acid nephropathy. Pathology 1987;19:143-149.
20.
Edwards JC, Bruno J, Key P, Cheng YW: Absence of chloride intracellular channel 4 (CLIC4) predisposes to acute kidney injury but has minimal impact on recovery. BMC Nephrol 2014;15:54.
21.
Jia T, Olauson H, Lindberg K, Amin R, Edvardsson K, Lindholm B, Andersson G, Wernerson A, Sabbagh Y, Schiavi S, Larsson TE: A novel model of adenine-induced tubulointerstitial nephropathy in mice. BMC Nephrol 2013;14:116.
22.
Santana AC, Degaspari S, Catanozi S, Dellê H, de Sá Lima L, Silva C, Blanco P, Solez K, Scavone C, Noronha IL: Thalidomide suppresses inflammation in adenine-induced CKD with uraemia in mice. Nephrol Dial Transplant 2013;28:1140-1149.
23.
Ali BH, Al-Salam S, Al Za'abi M, Waly MI, Ramkumar A, Beegam S, Al-Lawati I, Adham SA, Nemmar A: New model for adenine-induced chronic renal failure in mice, and the effect of gum acacia treatment thereon: comparison with rats. J Pharmacol Toxicol Methods 2013;68:384-393.
24.
Mori-Kawabe M, Yasuda Y, Ito M, Matsuo S: Reduction of NO-mediated relaxing effects in the thoracic aorta in an experimental chronic kidney disease mouse model. J Atheroscler Thromb 2015;22:845-853.
25.
Saus J, Wieslander J, Langeveld JP, Quinones S, Hudson BG: Identification of the Goodpasture antigen as the alpha 3(IV) chain of collagen IV. J Biol Chem 1988;263:13374-13380.
26.
Hopfer H, Maron R, Butzmann U, Helmchen U, Weiner HL, Kalluri R: The importance of cell-mediated immunity in the course and severity of autoimmune anti-glomerular basement membrane disease in mice. FASEB J 2003;17:860-868.
27.
Masaki T, Chow F, Nikolic-Paterson DJ, Atkins RC, Tesch GH: Heterogeneity of antigen expression explains controversy over glomerular macrophage accumulation in mouse glomerulonephritis. Nephrol Dial Transplant 2003;18:178-181.
28.
Xie C, Sharma R, Wang H, Zhou XJ, Mohan C: Strain distribution pattern of susceptibility to immune-mediated nephritis. J Immunol 2004;172:5047-5055.
29.
Xie C, Qin X, Jonnala G, Gong Y, Yan M, Zong P, Zhou XJ, Mohan C: Enhanced susceptibility to immune nephritis in DBA/1 mice is contingent upon IL-1 expression. Clin Immunol 2007;124:49-56.
30.
Nishida K, Watanabe H, Ogaki S, Kodama A, Tanaka R, Imafuku T, Ishima Y, Chuang VT, Toyoda M, Kondoh M, Wu Q, Fukagawa M, Otagiri M, Maruyama T: Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-associated acute kidney injury. Sci Rep 2015;5:14471.
31.
Petejova N, Martinek A: Acute kidney injury due to rhabdomyolysis and renal replacement therapy: a critical review. Crit Care 2014;18:224.
32.
Grange C, Moggio A, Tapparo M, Porta S, Camussi G, Bussolati B: Protective effect and localization by optical imaging of human renal CD133+ progenitor cells in an acute kidney injury model. Physiol Rep 2014;2:e12009.
33.
Loirat C, Frémeaux-Bacchi V: Atypical hemolytic uremic syndrome. Orphanet J Rare Dis 2011;6:60.
34.
Porubsky S, Federico G, Müthing J, Jennemann R, Gretz N, Büttner S, Obermüller N, Jung O, Hauser IA, Gröne E, Geiger H, Gröne HJ, Betz C: Direct acute tubular damage contributes to Shigatoxin-mediated kidney failure. J Pathol 2014;234:120-133.
35.
Keepers TR, Psotka MA, Gross LK, Obrig TG: A murine model of HUS: Shiga toxin with lipopolysaccharide mimics the renal damage and physiologic response of human disease. J Am Soc Nephrol 2006;17:3404-3414.
36.
Suyama K, Kawasaki Y, Miyazaki K, Kanno S, Ono A, Ohara S, Sato M, Hosoya M: The efficacy of recombinant human soluble thrombomodulin for the treatment of shiga toxin-associated hemolytic uremic syndrome model mice. Nephrol Dial Transplant 2015;30:969-977.
37.
Tesch GH, Nikolic-Paterson DJ: Recent insights into experimental mouse models of diabetic nephropathy. Nephron Exp Nephrol 2006;104:e57-e62.
38.
Nakagawa T, Sato W, Glushakova O, Heinig M, Clarke T, Campbell-Thompson M, Yuzawa Y, Atkinson MA, Johnson RJ, Croker B: Diabetic endothelial nitric oxide synthase knockout mice develop advanced diabetic nephropathy. J Am Soc Nephrol 2007;18:539-550.
39.
Landgraf SS, Silva LS, Peruchetti DB, Sirtoli GM, Moraes-Santos F, Portella VG, Silva-Filho JL, Pinheiro CS, Abreu TP, Takiya CM, Benjamin CF, Pinheiro AA, Canetti C, Caruso-Neves C: 5-Lypoxygenase products are involved in renal tubulointerstitial injury induced by albumin overload in proximal tubules in mice. PLoS One 2014;9:e107549.
40.
Tanaka-Kagawa T, Suzuki M, Naganuma A, Yamanaka N, Imura N: Strain difference in sensitivity of mice to renal toxicity of inorganic mercury. J Pharmacol Exp Ther 1998;285:335-341.
41.
Shimo T, Adachi Y, Yamanouchi S, Tsuji S, Kimata T, Umezawa K, Okigaki M, Takaya J, Ikehara S, Kaneko K: A novel nuclear factor κB inhibitor, dehydroxymethylepoxyquinomicin, ameliorates puromycin aminonucleoside-induced nephrosis in mice. Am J Nephrol 2013;37:302-309.
42.
Jamshidzadeh A, Heidari R, Mohammadi-Samani S, Azarpira N, Najbi A, Jahani P, Abdoli N: A comparison between the nephrotoxic profile of gentamicin and gentamicin nanoparticles in mice. J Biochem Mol Toxicol 2015;29:57-62.
43.
Leelahavanichkul A, Yan Q, Hu X, Eisner C, Huang Y, Chen R, Mizel D, Zhou H, Wright EC, Kopp JB, Schnermann J, Yuen PS, Star RA: Angiotensin II overcomes strain-dependent resistance of rapid CKD progression in a new remnant kidney mouse model. Kidney Int 2010;78:1136-1153.
44.
Peng H, Carretero OA, Alfie ME, Masura JA, Rhaleb NE: Effects of angiotensin-converting enzyme inhibitor and angiotensin type 1 receptor antagonist in deoxycorticosterone acetate-salt hypertensive mice lacking Ren-2 gene. Hypertension 2001;37:974-980.
45.
Kirchhoff F, Krebs C, Abdulhag UN, Meyer-Schwesinger C, Maas R, Helmchen U, Hilgers KF, Wolf G, Stahl RA, Wenzel U: Rapid development of severe end-organ damage in C57BL/6 mice by combining DOCA salt and angiotensin II. Kidney Int 2008;73:643-650.
46.
Chevalier RL, Forbes MS, Thornhill BA: Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy. Kidney Int 2009;75:1145-1152.
47.
Cochrane AL, Kett MM, Samuel CS, Campanale NV, Anderson WP, Hume DA, Little MH, Bertram JF, Ricardo SD: Renal structural and functional repair in a mouse model of reversal of ureteral obstruction. J Am Soc Nephrol 2005;16:3623-3630.
48.
Tapmeier TT, Brown KL, Tang Z, Sacks SH, Sheerin NS, Wong W: Reimplantation of the ureter after unilateral ureteral obstruction provides a model that allows functional evaluation. Kidney Int 2008;73:885-889.
49.
Puri TS, Shakaib MI, Chang A, Mathew L, Olayinka O, Minto AW, Sarav M, Hack BK, Quigg RJ: Chronic kidney disease induced in mice by reversible unilateral ureteral obstruction is dependent on genetic background. Am J Physiol Renal Physiol 2010;298:F1024-F1032.
50.
Wei Q, Dong Z: Mouse model of ischemic acute kidney injury: technical notes and tricks. Am J Physiol Renal Physiol 2012;303:F1487-F1494.
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2016
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