Table 2.
Summary of cre-driven mouse models (autosomal dominant polycystic kidney disease only)
| Model | Mutation Mechanism | Cre driver (Induction Agent/Disease Stage) | Expression Location | Phenotypes | Survival | Ref(s) |
|---|---|---|---|---|---|---|
| Conditional | ||||||
| Pkd1fl/fl | Deletion of exons 1–4 | Aqp2-cre (late) | Kidney (collecting ducts) at E13.5; testes and vas deferens | Cystic kidneys and increased kidney weight at 1 wk; severe PKD and increased BUN at 4 wk | Median, approximately 6 wk | 65,88 |
| Pkd1fl/– | Deletion of exons 2–6 | γGT(Ggt1)-cre (late) | Kidney (proximal tubule, collecting duct) at P7; liver and intestine | Progressive and severe PKD from P10 to P26 | <1 mo | 65,89,90 |
| Pkd1fl/fl | Deletion of exons 2–4 | Hoxb7-cre (late) | Kidney (collecting ducts) at E9.5; ureter, intestine, and spinal cord | Progressive and severe PKD at P7 and P15; enlarged kidneys (%KW/BW) and increased BUN | ND | 65,91,92 |
| Pkd1fl/fl and Pkd1fl/– | Deletion of exons 2–4 | Cdh16(Ksp)-cre (late) | Kidney (ureteric bud, mesonephric tubules) at E10.5 (distal tubules and collecting ducts); Wolffian and Mullerian ducts | Rapidly progressive PKD; enlarged kidneys (%KW/BW) at P4 and increased BUN at P7 | P14–P17 | 65,93 |
| Pkd1fl/fl | Deletion of exons 2–4 | Nes-cre (late) | Kidney at E12.5 (glomerulus, proximal tubules, loop of Henle, and distal tubules); heart and nervous system | Severe PKD, enlarged kidneys (%KW/BW), increased BUN, and widespread fibrosis at P49 | ND | 65,94 |
| Pkd1fl/– and Pkd1fl/fl | Deletion of exons 2–4 | Pkhd1-cre (late) | Kidney at E12.5 (collecting ducts); liver | Less severe disease and longer survival than Ksp-cre mice, severe PKD at P24 | ≥P24 | 65,93,95 |
| Pkd2fl/fl | Deletion of exons 3–4 | Pkhd1-cre (late) | Kidney at E12.5 (collecting ducts); liver | Severe PKD at P21 | ND | 65,95–97 |
| Pkd2f3/− | Deletion of exon 3 | γGT(Ggt1)-cre (early and late) | Kidney (proximal tubule, collecting duct) at P7; liver and intestine | Kidney cysts at 2 mo | ND | 98,99 |
| Conditional inducible | ||||||
| Pkd1fl/– | Deletion of exons 2–11 | Cdh16-cre/ERT2 (tamoxifen/early and late) | Kidney (collecting duct, loop of Henle, distal tubule) | Postnatal induction (P4), rapid cystic disease after 1 mo; postnatal induction (3–6 mo), mild cystic kidney disease after 3 mo | ND | 65,100 |
| Pkd1fl/fl and Pkd1fl/– | Deletion of exons 2–6 | Mx1-cre (pI-pC, IFNa and b dsRNA/early and late) | Kidney; heart, liver, and spleen | Postnatal induction (P7), severe PKD at 7 wk; postnatal induction (5 wk), focal kidney cysts 6–9 wk later, severe PKD and PLD at 13 mo | ND | 65,101 |
| Pkd1fl/fl and Pkd1fl/– | Deletion of exons 2–4 | Pax8-rtTA2S*M2 (doxycycline/late) | Kidney (proximal tubule, distal tubule, and collecting duct) | Postnatal induction (P11, 12, and 13), rapid cystic disease at P21 | ND | 65,95,102,103 |
| Pkd2fl/– | Deletion of exons 3–4 | Pax8-rtTA2S*M2 (doxycycline/early and late) | Kidney (proximal tubule, distal tubule, and collecting duct) | Postnatal induction (P28–42), severe cystic disease at 16 wk | ND | 102 |
| Inducible | ||||||
| Pkd1fl/fl | Deletion of exons 2–4 | Cag-cre/ER (tamoxifen/early and late) | All tissues | Postnatal induction (P2–P12), severe cystic kidney disease at P19; postnatal induction (P14–6 wk), slowly progressive cystic kidney disease at 6 mo, and liver cysts at 3 mo | ND | 98,104 |
| Pkd2f3/– | Deletion of exon 3 | Mx1-cre (pI-pC, IFNa and b dsRNA/early and late) | All tissues | Postnatal induction (4 wk), kidney, liver, and pancreatic cysts; postnatal induction (6 wk), 50% kidney and pancreatic cysts, 100% liver cysts | ND | 65,99 |
E, embryonic day; wk, week; ND, not described; P, postnatal day; PKD, polycystic kidney disease; mo, month; %KW/BW, percentage kidney weight/body weight; dsRNA, double-stranded RNA; BUN, blood urea nitrogen; PLD, polycystic liver disease; rtTA, reverse tetracycline-controlled transactivator.