| Co-Investigator(Kenkyū-buntansha) |
FUKAI Kzuyoshi Osaka City University Graduate School of Medicine, Department of Dermatology, Associate Professor, 大学院・医学研究科, 助教授 (20244642)
MAEDA Mitsuyo Osaka City University Graduate School of Medicine, The 1st Department of Anatomy, Lecturere, 大学院・医学研究科, 講師 (40122080)
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| Research Abstract |
Gene delivery into the brain via blood vessels is quite difficult because of the blood-brain-barrier (BBB). In the literature, a number of experiments of gene therapy for the brain have been done, but none of them has been successful. As it is speculated that microglia cells would go through BBB, we established a strain of cultured microglia cell from newborn mice brain for the vehicle of gene into the brain. The cells were labeled with a reporter gene of GFP and injected into the left ventricle of the heart of Sly mice. Sly mouse, the deficiency of β-glucuronidase, is a mouse model for human disease of mucopolysaccharidosis type VII, which is a systemic disorder including the brain caused by the accumulation of glycosaminoglycans. It is suggested that delivery of the deficient enzyme or the gene into each organ of this model mouse would improve the disease.
Our results showed that the exogenous microglia cells were seen only in the brain of the mice with the advanced stage of the disease, or in the ischemic brain. Thus, the cultured microglia cells could enter the brain though BBB only when BBB was injured. They could not found in the normal brain. However, when adenovirus vector with β-galactosidase gene was injected into the temporal surface vein of newborn mice with β-galactosidase deficiency, virus vectors could enter the brain and show β-galactosidase activity. Moreover, the accumulation of GM2 ganglioside was suppressed.
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