| First Author | Wu B | Year | 2016 |
| Journal | Biomed Res Int | Volume | 2016 |
| Pages | 7681259 | PubMed ID | 27872856 |
| Mgi Jnum | J:316245 | Mgi Id | MGI:6835326 |
| Doi | 10.1155/2016/7681259 | Citation | Wu B, et al. (2016) Altered Expression of EPO Might Underlie Hepatic Hemangiomas in LRRK2 Knockout Mice. Biomed Res Int 2016:7681259 |
| abstractText | Parkinson's disease (PD) is a severe neurodegenerative disorder caused by progressive loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain. The molecular mechanism of PD pathogenesis is unclear. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are a common genetic cause of familial and sporadic PD. However, studies on LRRK2 mutant mice revealed no visible dopaminergic neuronal loss in the midbrain. While surveying a LRRK2 knockout mouse strain, we found that old animals developed age-dependent hepatic vascular growths similar to cavernous hemangiomas. In livers of these hemangioma-positive LRRK2 knockout mice, we detected an increased expression of the HIF-2alpha protein and significant reactivation of the expression of the HIF-2alpha target gene erythropoietin (EPO), a finding consistent with a role of the HIF-2alpha pathway in blood vessel vascularization. We also found that the kidney EPO expression was reduced to 20% of the wild-type level in 18-month-old LRRK2 knockout mice. Unexpectedly, this reduction was restored to wild-type levels when the knockout mice were 22 months to 23 months old, implying a feedback mechanism regulating kidney EPO expression. Our findings reveal a novel function of LRRK2 in regulating EPO expression and imply a potentially novel relationship between PD genes and hematopoiesis. |
