Figure 3.

Gain of function by intraparenchymal infusion of En2 protein. A, After 14 d of infusion, En2 is detected in a large amount in a region encompassing the SN. Anterior sections are to the left and posterior to the right. B, Progressive loss of DA neurons in SN of En1+/− mice compared with WT expressed as the mean ± SD. At 3 weeks postnatal, the WT and En1+/− mice possess the same number of TH-positive cells in the SN. A decrease of ∼20% is observed at 8 weeks postnatal and of ∼28% at 16 weeks. Between 6 and 9 weeks postnatal, the En1+/− mice lose ∼10% of DA cells. C, Rescue of DA cell loss in En1+/− mice by En2 infusion above the SN. At 9 weeks postnatal, the control En1+/− mice have lost ∼20% of DA cells as compared with the WT (***p < 0.001). No significant difference in TH-positive cell numbers is found between WT infused with saline or WT infused with En2 (p = 0.4; NS). Infusion of En2 in En1+/− mice prevents cell loss in the SN. At 9 weeks postnatal, after 2 weeks of En2 infusion, the number of TH-positive neurons is increased significantly by ∼15% in En1+/− mice as compared with control (**p < 0.01) and is equivalent to the number of DA cells in WT infused with saline or En2.