The foxa2 Gene Controls the Birth and Spontaneous Degeneration of Dopamine Neurons in Old Age
Figure 4
Dopamine Neuron Loss in foxa2+/− Mice
(A and B) Dopamine neurons in a 24-mo-old wild-type mouse (A) and a foxa2+/− littermate (B). The mouse in (B) possessed a kinked posture and the other late-onset motor phenotypes. A significant loss of nigral dopamine neurons is easily observed on one side of the brain marked by a blue star in the foxa2+/− mouse.
(C and D) TH staining of the the ventral midbrain in older foxa2+/− animals without late onset behavioral abnormalities. Note that the dopaminergic system resembles the wild-type condition seen in (A).
(E) Nissl staining of wild-type and foxa2+/− mutant mice. Representative glia and neurons are highlighted with white and black arrows, respectively. Note the significant loss of normal neuronal morphologies in the mutant animal. Occasionally, a dysmorphic cell, highlighted here with a purple arrow, can be seen in the mutant, but not the wild-type brain.
(F) Ventral tier dopamine neurons, stained for RALDH1 (red), are selectively lost in foxa2+/− animals. In this animal, nigral dopamine neurons are almost completely lost on the left side (marked by the blue star), whereas the right side (marked by the red sun) is much less affected (note that these are coronal sections, presented as if the animal were facing the viewer, so that the left side of the animal is on the viewer's right side.
(G) Quantitation of dopamine neurons in the SN and VTA of wild-type (n = 3) and foxa2+/− (n = 3) mice. The number of dopamine neurons in the mutant SN (2,765.0 ± 750.5) is substantially smaller than in the control SN (7,344.3 ± 197.9). In contrast, the number of the dopamine neurons in the VTA is roughly the same in wild-type (9,922.0 ± 375.7) and mutant mice (10,064.7 ± 355.4).
(H) The percentage of RALDH1-expressing neurons in the SN is reduced in foxa2+/− mutants as compared to wild-type controls.