RESUMEN
Aim To investigate TH and GDNF genes expression and regulation of lentivirus ( Lv-TH-GDNF ) based on improved Tet-On system and the effect of the Lv-TH-GDNF intrastriatal transfer on a rat Parkinson’ s disease( PD) model. Methods 1. HeLa cells were infected by obtained Lv-TH-GDNF and rtTA2 s-M2 vi-rus. The expression of tyrosine hydroxylase ( TH ) and glial cell line-derived neurotrophic factor( GDNF) genes was induced by doxycycline( Dox) which was examined by Western blot. 2. The Lv-TH-GDNF together with rtTA2 s-M2 viruses were injected into lesion-side stria-tum of a rat PD model, and the expression of GDNF and TH genes was induced by Dox. Then, the effects of Lv-TH-GDNF were evaluated by the apomorphine-induced rotational behavior, the number of dopaminer-gic neurons in substantia nigra,DA and DOPAC levels in the lesion-side striatum. In addition, Western blot was performed to check the expression of TH and GD-NF genes in the transplanted striatum. Results 1. In vitro studies on HeLa cells, Western blot showed clear protein bands of TH and GDNF in the Dox-positive group, but not in the Dox-negative group. 2. In vivo experiments in animals, the results showed that, 4 weeks after transplantation, the apomorphine-induced turning effect was significantly improved ( P<0 . 01 ) , the number of TH-positive cells in the lesion-side sub-stantia nigra pars compacta as well as the content of DA and DOPAC, the protein level of GDNF and TH genes in the lesion-side striatum was significantly in-creased ( P<0 . 01 ) , each of which was only in Lv-TH-GDNF+rtTA2 s-M2+Dox-treated rats as compared with PBS-treated rats. Conclusion The expression of TH and GDNF genes in Lv-TH-GDNF based on im-proved Tet-On system is effectively regulated by tetra-cycline antibiotics without basal activity in vitro, and the intrastriatal transfer of which has certain therapeutic effect on PD rats.
RESUMEN
PURPOSE: Medullary sponge kidney (MSK) is a rare congenital disease characterized by diffuse ectasia or dilatation of precalyceal collecting tubules. MSK incidence and prevalence in the general population is uncertain and only a few patients are reported especially in the pediatric age. There has been increasing reports of patients with MSK who have other malformative disorders. Also several case reports concerning about etiological association of some genes. METHODS: Collaborative study through nation-wide survey was done to investigate the incidence and etiological association of some genes such as GDNF gene, ATP6V1B1, ATP6V0A4 gene in developing MSK in Korean children. RESULTS: Four cases of MSK who have various other malformative disorders were collected. There are no mutations of GDNF gene, ATP6V1B1, ATP6V0A4 gene in all patients. CONCLUSION: MSK is one of the very rare diseases in pediatric age. The etiological association of GDNF gene , ATP6V1B1, ATP6V0A4 gene in developing MSK in Korean children is not proved.