Conditional disruption of <i>Tsc1</i> results in polycystic kidney disease.

<p><i>Tsc1</i>^<i>fl/fl</i> mice were bred to <i>Mb1Cre</i>⁺ mice. (A) Representative gross pictures of <i>Tsc1</i>^<i>fl/fl</i> <i>Mb1Cre</i>⁺ and WT kidneys showing that loss of <i>Tsc1</i> results in kidney enlargement in 20-week old mice. (B) Representative histology images of <i>Tsc1</i>^<i>fl/fl</i> <i>Mb1Cre</i>⁺ kidneys showing development of polycystic kidney disease at 20 weeks of age. (C) Kidney-to-brain ratio graph showing ratios at 5, 10, and 20 week old <i>Tsc1</i>^<i>fl/fl</i> <i>Mb1Cre</i>⁺ and WT mice showing a gradual increase in kidney-to-brain weight ratio in <i>Tsc1</i>^<i>fl/fl</i> <i>Mb1Cre</i>⁺ kidneys. (n = 3 each genotype, p-values are shown) (D) Survival graph of <i>Tsc1</i>^<i>fl/fl</i> <i>Mb1Cre</i>⁺ (solid black line), <i>Tsc1</i>^<i>fl/+</i> <i>Mb1Cre</i>+ (sold blue line), and rapamycin treated <i>Tsc1</i>^<i>fl/fl</i> <i>Mb1Cre</i>⁺ (dotted red line) showing that polycystic kidney disease is fatal, but that disease induction can be blocked by inhibiting mTOR with Rapamycin. Rapamycin diet was started at weaning and continued until euthanasia. (E) Immunoblots of proteins isolated from whole kidney lysates from 12-week old mice showing increased p-S6R and p-4EBP indicative of increased mTORC1 activation, and increased p-Erk in <i>Tsc1</i>^<i>fl/fl</i> <i>Mb1Cre</i>⁺ relative to WT kidney tissue.