Heterozygous CDKL5 Knockout Female Mice Are a Valuable Animal Model for CDKL5 Disorder

Figure 4

Impaired hippocampus-dependent learning and memory in Cdkl5 +/− female mice. (a) Spatial learning assessed using the Morris water maze. Cdkl5 +/− () and Cdkl5 −/− () mice showed an increased latency to find the platform over the 5-day learning period compared to the Cdkl5 +/+ () mice. (b, c) Maximum (b) and average (c) swim speed during the learning phase in mice as in (a). (d) Percentage of floating, defined as the percentage of time swimming at less than 4 cm/s during the learning phase in mice as in (a). (e–h) On day 6 (probe test), the platform was removed and spatial memory was assessed by evaluating different parameters. Cdkl5 +/− and Cdkl5 −/− mice showed an increased latency to enter the former platform zone (e), a reduced frequency to enter (f), and time spent in the quadrant (g) in which the platform had been located during the learning period. In addition, Cdkl5 +/− and Cdkl5 −/− mice swam a larger distance from the former platform (h) compared to the Cdkl5 +/+ mice, indicating defects in spatial memory. Values represent . , , and as compared to the Cdkl5 +/+ female mice; as compared to the Cdkl5 +/− female mice (dataset in a); , , and as compared to the Cdkl5 +/+ or Cdkl5 +/− female mice (dataset in b–h), Fisher’s LSD test after ANOVA; datasets in (d), Dunn’s test after Kruskall-Wallis).

(a)

(b)

(c)

(d)

(e)

(f)

(g)

(h)