Table 1.

Different PKD1 inactivation and injury strategies with iKsp-Pkd1del mice lead to different phenotypes

Tam/Injury ProtocolOrigin of CystsShort Description of Renal Cystic PhenotypeReferences
Tam at P4 (200 mg/kg to lactating mother; pups receive Tam through mother’s milk)DT > CD > PTRapid formation of numerous large cysts within 1 mo19
Tam at P10 (6 mg/kg oral)DT > CD > PTRapid formation of numerous large cysts within 1 mo66
Tam at P18 (150 mg/kg oral)DT = CD = PTSynchronized formation of many cysts; renal failure around 10–12 wk after Tam66
Low-dose Tam at P40 (10 mg/kg oral)PT > DT > CDVery few cysts within the first 6 mo after Tam; first cysts induce clustered formation of new cysts; severe PKD around 10 mo after Tam20
Low-dose Tam at P40 (10 mg/kg oral) + DCVC- (15 mg/kg intraperitoneal) and/or unilateral nephrectomy–induced injuryPT > DT > CDSimilar PKD phenotype compared with mice only treated with low-dose Tam at P40 but slightly faster20
Tam at P40 (200 mg/kg oral)PT > DT > CDSynchronized formation of many cysts, renal failure around 14–16 wk after Tam20,64,69,75
Tam at P40 (200 mg/kg oral) + unilateral nephrectomy–induced injuryPT > DT > CDSimilar PKD phenotype compared with mice only treated with Tam at P40 but about 30% faster20
Tam at P90 (200 mg/kg oral)PT > DT > CDSynchronized formation of many cysts; renal failure around 22 wk after Tam19,32
Tam at P90 (200 mg/kg oral) + DCVC-induced injury (15 mg/kg intraperitoneal)PT > DT > CDSimilar PKD phenotype compared with mice only treated with Tam at P90 but about 40% faster32
  • At various P days, tamoxifen (Tam) treatments (always on 3 consecutive days starting from the indicated ages using the indicated dosages) were performed to inactivate Pkd1 in iKsp-Pkd1del mice (all on C57BL/6 background). In some strategies, renal injury by injection of the nephrotoxic compound 1,2-dichlorovinyl-cysteine (DCVC) or unilateral nephrectomy was performed, and/or a lower dose of Tam (low-dose Tam) was administered to reduce the number of Pkd1-deficient cells. These protocols are indicated in column 1. In column 2, the relative abundance of cysts is shown in proximal tubules (PTs), distal tubules (DTs), and collecting ducts (CDs). Also, a short description of the cystic phenotypes and the references are given. Notably, although the Pkd1 mutation and genetic background are always the same, the renal cystic phenotype varied considerably depending on the experimental procedure performed. Detailed descriptions of various other rodent models for PKD has been reviewed elsewhere by Happé et al.29