Fig. 8.

Decrease in KCC2 expression leads to seizures and lethality. A: pentylenetetrazole (PTZ)-induced seizures in 6-wk-old wild-type and heterozygote KCC2-null mice. Two groups of mice (21 wild-type and 21 heterozygotes) were injected daily with 60 mg/kg PTZ for a total of 4 days. The number of mice exhibiting seizures scoring >3 within 1 h after the injection are represented. [Modified from Ref. 156, with permission.] B: Kaplan-Meier plots of KCC2b knockouts and CAMKIIα-driven inducible KCC2 knockouts [where mice were fed with doxycycline chow (200 mg/kg, BioServ, Frenchtown, NJ) since conception until doxycycline withdrawal at postnatal day 40 (P40)]. Lethality occurred between P110 and P130, indicating both slow elimination of the drug and a slow decrease in KCC2 expression. C: Western blot analysis of KCC2 expression at P60 in hindbrain and forebrain of a control and an inducible KCC2 knockout mouse after 2 wk doxycycline withdrawal.