Fig. 5. Nestin-Cre conditional
v mutants develop seizures and motor
dysfunction, and die prematurely. (A,B) Motor dysfunction in 3-week-old
Nestin-Cre conditional
v mutants. When lifted by their tails, control
mice (A) extend and flail their limbs. Conditional
v mutants (B)
retract their limbs and remain immobile. The conditional
v mutant in B
also displayed episodic signs of seizures and associated temporary loss of
consciousness (data not shown). (C,D) Hematoxylin and Eosin-stained coronal
sections from cerebral cortices of three-week-old control (C) and mutant (D)
brains from mice shown in A,B. Regions of cerebral microhemorrhage are present
in the mutant brains (arrow in D). (E,F) Cross-sections from control (E) and
mutant (F) spinal cords. Focal regions of microhemorrhage are found throughout
spinal cord of conditional
v mutants (arrow in F). (G,H) Pictures of
7-month-old control (G) and mutant (H) animals. The mutant displays hind-limb
spasticity and abnormal posture. (I) Footprint analysis performed using 4- to
5-month-old control (left panel) and mutant (right panel) mice; hind paws
painted blue and fore paws painted red. The conditional mutant drags its
hindlimb (right). (J) Rotarod analyses of control and Nestin-Cre conditional
v mutants as described in the Materials and methods. The times animals
remained on the rod rotating at an increasing speed versus the trial number is
plotted. A significant reduction (P<0.005 for all trials) in time
spent on the rod is observed in mutant (n=7) versus control mice
(n=9).