Background: Alkaline phosphatase has 4 isozymes, tissue non-specific alkaline phosphatase (TNAP), placental alkaline phosphatase (PLAP), intestinal alkaline phosphatase and germ-cell alkaline phosphatase. Hypophosphatasia (HPP) is an inherited skeletal disease caused by mutations of the gene encoding TNAP. Although TNAP is expressed in various tissues, the primary HPP symptoms appear in bones and teeth. The clinical severity of HPP varies widely from the most severe (perinatal, infantile and childhood) to the mildest forms (adult, and odonto-hypophosphatasia). We reported that gene therapy using a single injection of lentiviral vector expressing bone-targeted TNAP (TNAP-D 10 ) is effective in preventing all the skeletal of HPP in TNAP knockout (Alpl −/− ) mice as the model of infantile HPP. Objective: In this study we focus on evaluating the efficacy of treatment with gene therapy on the bone and teeth using TNAP-D 10 and also we investigate the feasibility of gene therapy using bone-targeted PLAP (PLAP-D 10 ). Methods and Findings: We used

Hypophosphatasia(HPP)is caused by mutations in the gene encoding tissue-nonspecific alkaline phosphatase (ALPL). HPP patients develop deficient calcification of bones and teeth including defects in cementum, dentin, and enamel and the characteristic premature loss of primary teeth. Here, we investigated the enamel defects of knockout(Alpl -/-)mice compared with that of control wild type(Alpl +/+ )mice.No alkaline phosphatase (ALP) activity was detected by specific staining in the first molar germ of Alpl -/-mice on postnatal day 5. Hematoxylin and eosin staining revealed that the enamel layer in Alpl -/-mice was thin, undulated, and rugged. Furthermore, Alpl Our study suggests that ALP may have involvement in EMPs and enamel defects in Alpl -/-mice is caused by ameloblasts disorder. Furthermore, our study advances elucidation of the mechanisms that underlie enamel development, and will support establish the causes of enamel defects of HPP patients.