Table 1 |.
Progression of cystic disease in Pkd1RC/RC mice across each genetic background
| Endpoint | B6 | BC | F1(BC/B6) | 129 | F1(129/B6) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
| |||||||||||||||
| KW/BW, % | M | F | M | F | M | F | M | F | M | F | |||||
| 1 mo | 5 | 5 | 1.62 ± 0.13 | 5 | 5 | 2.58 ± 0.93d | 5 | 5 | 1.96 ± 0.33 | 5 | 5 | 2.45 ± 1.07 | 5 | 5 | 1.80 ± 0.32 |
| 3 mo | 5 | 5 | 1.85 ± 0.26 | 5 | 5 | 3.24 ± 0.86f | 5 | 5 | 1.92 ± 0.22 | 5 | 5 | 3.08 ± 0.84e | 6 | 4 | 2.64 ± 1.06 |
| 6 mo | 5 | 5 | 1.98 ± 0.28 | 5 | 5 | 3.73 ± 0.58a.f | 5 | 5 | 2.40 ± 0.37 | 5 | 5 | 4.93 ± 1.89c.f | 3 | 6 | 3.59 ± 1.01c.f |
| 9 mo | 5 | 5 | 2.24 ± 0.26a | 5 | 5 | 3.98 ± 0.96b.f | 5 | 5 | 3.60 ± 0.63c.e | 5 | 5 | 4.10 ± 0.88b.f | 5 | 5 | 2.90 ± 1.24a |
| 12 mo | 5 | 5 | 3.37 ± 1.06c | 5 | 5 | 4.10 ± 1.14b | 5 | 5 | 3.42 ± 0.49c | 5 | 5 | 4.27 ± 0.51b | 6 | 4 | 2.45 ± 0.71 |
| Cystic area, % | |||||||||||||||
| 1 mo | 5 | 5 | 3.13 ± 1.10 | 3 | 5 | 18.07 ± 5.59f | 4 | 5 | 5.10 ± 5.10 | 5 | 5 | 15.56 ± 6.72f | 5 | 5 | 7.02 ± 4.00 |
| 3 mo | 5 | 5 | 4.20 ± 2.15 | 5 | 5 | 18.15 ± 6.06f | 5 | 5 | 9.87 ± 5.49 | 5 | 4 | 26.48 ± 14.37a.f | 6 | 3 | 8.46 ± 3.73 |
| 6 mo | 5 | 5 | 4.83 ± 3.61 | 5 | 5 | 23.23 ± 4.71f | 4 | 5 | 9.33 ± 3.44 | 5 | 5 | 30.23 ± 10.20b.f | 2 | 6 | 17.31 ± 4.64b,f |
| 9 mo | 4 | 4 | 5.54 ± 3.55 | 4 | 5 | 21.02 ± 2.47f | 5 | 5 | 17.57 ± 3.99c,f | 4 | 5 | 25.14 ± 4.20f | 5 | 5 | 12.06 ± 7.28d |
| 12 mo | 5 | 5 | 14.43 ± 8.02c | 5 | 4 | 27.35 ± 10.75a,f | 5 | 5 | 16.02 ± 4.29c | 4 | 5 | 18.01 ± 5.64 | 6 | 4 | 16.95 ± 8.36c |
| Cyst number | |||||||||||||||
| 1 mo | 5 | 5 | 17 ± 8 | 3 | 5 | 94 ± 33d | 4 | 5 | 35 ± 22 | 3 | 5 | 62 ± 22 | 5 | 5 | 24 ± 9 |
| 3 mo | 3 | 4 | 19 ± 6 | 5 | 5 | 148 ± 55f | 4 | 5 | 62 ± 30 | 5 | 4 | 93 ± 27d | 4 | 5 | 54 ± 35 |
| 6 mo | 5 | 5 | 44 ± 38 | 5 | 5 | 205 ± 34c,f | 4 | 5 | 106 ± 57b,d | 5 | 5 | 166 ± 49c,f | 2 | 6 | 87 ± 26 |
| 9 mo | 2 | 4 | 75 ± 36c | 4 | 6 | 288 ± 81c.f | 4 | 5 | 216 ± 42c,f | 2 | 6 | 221 ± 46c,f | 5 | 5 | 116 ± 46b,e |
| 12 mo | 5 | 5 | 80 ± 30c | 5 | 5 | 197 ± 51b,f | 5 | 5 | 213 ± 44c,f | 4 | 5 | 201 ± 54c,f | 6 | 4 | 170 ± 67c,f |
| BUN, mg/dl | |||||||||||||||
| 1 mo | 5 | 5 | 17.7 ± 3.0 | 3 | 5 | 21.3 ± 4.0 | 5 | 5 | 16.4 ± 3.4 | 5 | 5 | 19.0 ± 4.2 | 3 | 3 | 15.5 ± 2.3 |
| 3 mo | 4 | 5 | 24.1 ± 1.6 | 5 | 5 | 20.5 ± 4.5 | 5 | 5 | 18.0 ± 3.3 | 5 | 5 | 23.0 ± 4.2 | 7 | 2 | 23.2 ± 2.6a |
| 6 mo | 5 | 5 | 24.0 ± 2.8 | 2 | 5 | 23.4 ± 3.3 | 5 | 5 | 18.6 ± 4.1 | 5 | 5 | 27.3 ± 4.9b | 6 | 2 | 30.4 ± 3.3b |
| 9 mo | 4 | 3 | 24.6 ± 5.2 | 5 | 5 | 32.1 ± 7.6 | 5 | 5 | 21.0 ± 4.5 | 3 | 5 | 30.5 ± 5.0c | 3 | 4 | 24.2 ± 3.5a |
| 12 mo | 5 | 5 | 30.5 ± 13.7c | 5 | 5 | 36.5 ± 16.7b | 5 | 5 | 23.0 ± 5.6b,d | 4 | 5 | 30.4 ± 8.1c | 7 | 2 | 35.0 ± 9.1c |
| Fibrotic area, (%) | |||||||||||||||
| 1 mo | 3 | 4 | 1.18 ± 0.78 | 3 | 3 | 1.10 ± 0.74 | 3 | 3 | 0.60 ± 0.44 | 3 | 5 | 0.65 ± 0.53 | 3 | 3 | 0.19 ± 0.15 |
| 3 mo | 3 | 3 | 1.16 ± 0.71 | 3 | 3 | 1.18 ± 1.57 | 3 | 4 | 0.58 ± 0.43 | 3 | 5 | 1.47 ± 0.52 | 3 | 2 | 1.34 ± 0.55 |
| 6 mo | 3 | 3 | 1.59 ± 0.63 | 3 | 3 | 2.37 ± 0.96 | 3 | 3 | 1.06 ± 0.71 | 5 | 5 | 3.45 ± 1.77 | 3 | 3 | 0.98 ± 1.06 |
| 9 mo | 3 | 3 | 4.23 ± 2.01b | 3 | 3 | 4.42 ± 4.05 | 3 | 3 | 5.02 ± 3.57a | 5 | 5 | 6.09 ± 2.50c | 3 | 4 | 3.44 ± 2.57 |
| 12 mo | 3 | 3 | 10.46 ± 2.91c | 3 | 4 | 8.64 ± 3.98c | 3 | 3 | 6.29 ± 3.96b,d | 5 | 5 | 14.17 ± 4.72c,d | 7 | 2 | 5.82 ± 4.17b,e |
| cAMP, pmol/mg protein | |||||||||||||||
| 1 mo | 5 | 5 | 6.96 ± 3.97 | 3 | 5 | 3.83 ± 1.70 | 5 | 4 | 9.57 ± 1.86 | 4 | 3 | 13.17 ± 5.22 | 5 | 5 | 7.34 ± 2.10 |
| 3 mo | 5 | 5 | 5.72 ± 2.10 | 5 | 5 | 3.81 ± 2.30 | 5 | 5 | 7.21 ± 1.29 | 3 | 3 | 14.26 ± 5.67d | 5 | 5 | 4.29 ± 0.94 |
| 6 mo | 5 | 4 | 7.90 ± 2.68 | 5 | 5 | 8.82 ± 5.06 | 4 | 5 | 9.71 ± 5.32 | 3 | 2 | 31.48 ± 10.71a,f | 4 | 5 | 10.35 ± 4.46 |
| 9 mo | 4 | 4 | 16.49 ± 6.38c | 5 | 5 | 11.56 ± 2.2a | 5 | 5 | 15.10 ± 5.81 | 4 | 3 | 45.31 ± 12.75c,f | 3 | 4 | 11.25 ± 4.79a |
| 12 mo | 2 | 5 | 18.40 ± 6.49c | 5 | 5 | 23.08 ± 10.13c | 5 | 5 | 19.02 ± 10.26b | 1 | 3 | 38.02 ± 12.75b,f | 7 | 2 | 7.76 ± 2.03 |
| TKV, mm3 | |||||||||||||||
| 1 mo | 3 | 7 | 442 ± 92 | 2 | 1 | 1022 ± 224e | 0 | 1 | 403 | 5 | 5 | 597 ± 201 | 5 | 5 | 448 ± 98 |
| 3 mo | 2 | 8 | 603 ± 145 | 1 | 2 | 1375 ± 247f | 3 | 4 | 735 ± 177 | 5 | 5 | 1175 ± 431c,f | 5 | 5 | 999 ± 267c,f |
| 6 mo | 3 | 7 | 745 ± 196a | 1 | 1 | 1225 ± 169 | 0 | 1 | 1021 | 2 | 4 | 1683 ± 165c,f | 5 | 5 | 1060 ± 410c,d |
| 9 mo | 5 | 4 | 750 ± 100a | 0 | 1 | 2122 | 0 | 0 | NA | 2 | 5 | 1876 ± 303c,f | 5 | 5 | 1479 ± 239c,f |
| 12 mo | 2 | 5 | 919 ± 163c | 0 | 0 | NA | 0 | 0 | NA | 2 | 1 | 1660 ± 273c,f | 6 | 4 | 1312 ± 269c,e |
129, 129S6/SvEvTac; ANOVA, analysis of variance; B6, C57BL/6J; BC, BALB/cJ; BUN, blood urea nitrogen; cAMP, cyclic adenosine monophosphate; KW/BW, kidney weight/body weight; NA, not available; Pkd1RC/RC mice, mice homozygous for the PKD1 hypomorphic allele p.Arg3277Cys; TKV, total kidney volume.
One-way ANOVA followed by Dunnett’s multiple comparison test compared to 1-month mice within each background:
P < 0.05,
P < 0.01,
P < 0.001. Two-way ANOVA followed by Dunnett’s multiple comparison test indicating significant difference from age-matched B6 mice:
P < 0.05,
P < 0.01,
P < 0.001. Numbers of male (M) and female (F) mice for each analysis are shown. Statistical analysis was performed only on groups that contained n ≥ 3.