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. 2018 Sep 12;2018:1462802. doi: 10.1155/2018/1462802

Table 1.

Genetically altered mice used in the investigation of cisplatin nephrotoxicity.

    age              
  background  sex   cisplatin          
GEM model (breeder) N dose end mortality S measured parameters Ref.
    25-30g            
  129/SV male 10 mg/kg       BUN, Cr, Cr clearance, HO-1, p21mRNA  
CYP2e1−/− (NIH) N=10 ip D3 nr ↓ and protein, TUNEL [74]
Oct1−/−    8-12wk       ns    
Oct2−/−  FVB male 10 mg/kg     ns    
Oct1/2/−/− (Taconic) N=11 ip D3 nr ↓ Histology, Cr, BUN, ALT↑, ALP↓ [35]
    6-10wk            
  C57BL/6 male, female 15 mg/kg          
GstP1/P2−/− (UK) N=5-9 ip D5 0% ↓ Cr, ATN, WBC [75]
    11-15wk         D3:BUN, Cr, AST  
Mate1−/−   male 15 mg/kg       mortality  
(pyrimethamine)∗ C57BL/6 N=6 ip D6 100% ↑   [41]
Mdk−/− 129SV 8-12wk 12 mg/kg D7 nr ↓ ↓BUN, TUNEL, histology, ≈leukocytes [76]
    male ip       infiltration (neutrophil, macrophages, Tcells),  
    N=6         Bcl-2, KC protein, MCP-1, MIP-2  
    8-10wk         Survival, histology, BUN, Cr, leukocyte  
    male 15 mg/kg       infiltration, TUNEL, TNFα, ICAM1 mRNA,  
PI3Kγ−/− C57BL/6 N=25 ip D5 44% ↑ proteins, p-Akt, p-Bad [77]
    10-12wk            
  B6x129/SF2/J male 20 mg/kg          
E2F1−/− (Jax) N=6 ip D3 nr ↓ ↓BUN, Cr, histology, [78]
p53−/−   nr N=6 20 mg/kg          
(pifithrin-α)∗ (Jax) ip D3 nr ↓ ↓BUN, Cr, histology [79]
p53−/−   C57BL/6J 8-10 wk, male 30 mg/kg          
(pifithrin-α)∗ (Jax) N=22-29 ip D3 nr ↓ ↓BUN, Cr, histology [80]
  C57BL/6 8-10wk, male 30 mg/kg          
Bax−/− (Jax) N=3-8 ip D3 nr ↓ BUN, Cr, ATN, TUNEL, cytochrome C [81]
              Histology, BUN, Cr, neutrophils infiltration,  
  C57BL/6 8-10wk, male         TUNEL, Casp-1,-3,-8,-9 activity, IL-1β  
Casp-1−/− (Japan) N=4-15 30 mg/kg D3 nr ↓   [82]
    8-15 wk, male         BUN, histology, TUNEL  
p21-/- nr N=5-6 20 mg/kg D3 30% ↑   [83]
HO-1+/-   12-16wk 20 mg/kg     ≈    
HO-1−/− nr N=8 ip D3   ↑ ↓BW, ↑BUN [84]
  C57BL/10Sn 6-8 wk   D3        
C5−/− (Jax) male     ↓ BUN, Cr, histology, MDA, MPO, [85]
  BALB/c N=5-12 20 mg/kg     nitrotyrosine, TNF-α, IL-1β, ICAM-1, casp-3,8,9, STAT3, NF-κB
C5aR−/− (Jax) SPF ip   ↓  
  DBA/1lacJ x 3-4 months         BW, histology, BUN, Cr, Hct,  
mPGES-1−/− C57BL/6 x male 20 mg/kg       TNFα, IL-1β;  
(celecoxib)∗ 129/SV N=6-16 ip D3 nr ↓   [86]
TNFα -/-    8-9 wk         Histology, BUN, leukocyte infiltration  
(GM6001, B6129SF2/J male            
Pentoxifylline)∗ (Jax) N=7 20 mg/kg D3 nr ↓   [87]
  C57BL/6 8-10wk, male         Histology, BUN, Cr, neutrophil infiltration,  
TLR4−/− (Jax) N=4-7 20 mg/kg D3 nr ↓ cytokines [88]
        D1     Kidney: ↑neutrophils, CXCL1, CXCL2,  
    8-10wk          ≈CD4+, ↓CD4+CD25+, Foxp3  
N=6-10
TLR9−/− C57BL/6   20 mg/kg D3 nr ↑ Blood: ↑BUN; Kidney: ↑histology score [72]
  C57BL/6 8-10 wks 15mg/kg       Blood: ≈BUN; Kidney: ≈histology score  
Tcrd−/− (Jax) ♂, N=9 ip D4 nr ns   [67]
Asc−/− C57BL/6 8-10 wk, male 15mg/kg       Blood: ↓BUN;  
TLR2−/− (Jax) N=5 ip D4 nr ↓ Kidney: ↓histology score, IL-17A, IL-1β [67]
  C57BL/6 8-10 wk, male 15mg/kg       Blood: ↓BUN; Kidney: ↓histology score  
Rorγt-/- (Jax) N=9 ip D4 nr ↓   [67]
    8-10 wk,   D1     Kidney:↓neutrophils, ≈CD4+ T cells, CXCL1,  
IL-17A−/−   C57BL/6 male 15mg/kg       CXCL2, CCL2, CCL5  
(anti-IL-17A)∗ (Jax) N=8 ip D4 nr ↓ Blood: ↓BUN; Kidney: ↓histology score [67]
  C57BL/6 8-10 wk, male         Histology, BUN, Cr,  
IL-6 −/− (Jax) N=4-6 30 mg/kg D3 nr ns   [65]
    10-12wk,         ↓Mortality,  
  C57BL/6J male         ↑BUN [89, 90]
IL-6−/− (Jax) N=9-18 30 mg/kg D8 47% ↓∗∗  
      6-8 wk             Morality, Cr, histology, MPO,     
nu/nu 
B6.Cg-Foxn1nu  		 C57BL/6  male             TNFα, IFN-γ,IL-1β, KC     
(T-cell transfer)∗ (Jax) N=3-14 40 mg/kg  D3 0% ↓   [69]
    6-8wk   D2 6%   Mortality, BUN, Cr, histology, macrophage  
nu/nu 
(CD4+CD25+Treg		 BALB/c male   D3 31%   infiltration (F4/80 positive cells), TNFα, IL-1β  
transfer) (South Korea) N=16 40 mg/kg D4 13% ↓   [70]
CD4−/−   B6129S2 6-8 wk, male         ↓Morality, Cr, histology  
B6.129S2-Cd4tm1Mak (Jax) N=16 40 mg/kg D3 38% ↓   [69]
    8-10wk         Blood: ↓Cr; Kidney: ↓histology score  
CD4−/− 
CD4 tm1Mak		 C57BL/6 male            
GK1.5 monoclonal AB∗ (Jax) N= 25 mg/kg D3 nr ↓   [51]
    8-10wk 10 mg/kg       Blood: ≈BUN, Cr; Kidney: ≈caspase-3,  
CD4−/− 
CD4 tm1Mak		 C57BL/6 male per week       TUNEL,≈ IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, CXCL1, TNFα, IFN-γ  
GK1.5 monoclonal AB∗ (Jax) N=10 for 4 wks 4wks nr ns [91]
CD8−/−   B6129S2 6-8 wk, male         Mortality, Cr, histology  
B6.129S2-Cd8atm1Mak (Jax) N=16 40 mg/kg D3 56% ↓   [69]
  C57BL/6 8-10wk, male         Blood: ↓Cr; Kidney:↓histology score,  
CXCR2−/− (Jax) N=4 25 mg/kg D3 nr ↓ apoptosis [51]
  C57BL/6 (wt) 8-10wks 12 mg/kg       Blood: ↓BUN, serum TNF; Kidney:  
KitW-sh/W-sh (Jax) N=7 ip D4 0% ↓ ↓histology score [71]

∗A pharmacological inhibitor of particular gene/protein. ∗∗IL-6 deficiency accelerates the development of nephrotoxicity at the early stage but resists the progress of systemic injury [89].

N: number; S: susceptibility to cisplatin toxicity; ip: intraperitoneally; D: day; ≈: ns; ↓: decrease; ↑: increase; BUN: blood urea nitrogen; Cr: serum creatinine; GFR: glomerular filtration rate; ATN: acute tubular necrosis; BW: body weight; WBC: white blood cells; Hct: hematocrit; TNFα: tumor necrosis factor alpha; IL: interleukin; IFNγ: interferon gamma; MCP-1: monocyte chemoattractant protein-1; HO-1: heme oxygenase-1; ICAM-1: intracellular adhesion molecule-1; TLR4: toll like receptor 4; COX: cyclooxygenase; Casp3: caspase 3; KC: keratinocyte-derived chemokine; MPO: myeloperoxidase; SOD: superoxide dismutase; CAT: catalase; GSH: glutathione; GPx: glutathione peroxidase; GR: glutathione reductase; GST: glutathione S transferase; MDA: malondialdehyde; ALT: alanine transaminase; AST: aspartate transaminase; ALP: alkaline phosphatase; Cas3: caspase 3; Cas9: caspase 9; CXCL: chemokine (C-X-C motif) ligand; CCL: chemokine (C-C motif) ligand.