| First Author | Yamamoto S | Year | 2011 |
| Journal | J Bone Miner Res | Volume | 26 |
| Issue | 1 | Pages | 135-42 |
| PubMed ID | 20687159 | Mgi Jnum | J:179855 |
| Mgi Id | MGI:5304251 | Doi | 10.1002/jbmr.201 |
| Citation | Yamamoto S, et al. (2011) Prolonged survival and phenotypic correction of Akp2(-/-) hypophosphatasia mice by lentiviral gene therapy. J Bone Miner Res 26(1):135-42 |
| abstractText | Hypophosphatasia (HPP) is an inherited systemic skeletal disease caused by mutations in the gene encoding the tissue-nonspecific alkaline phosphatase (TNALP) isozyme. The clinical severity of HPP varies widely, with symptoms including rickets and osteomalacia. TNALP knockout (Akp2(-/-)) mice phenotypically mimic the severe infantile form of HPP; that is, TNALP-deficient mice are born with a normal appearance but die by 20 days of age owing to growth failure, hypomineralization, and epileptic seizures. In this study, a lentiviral vector expressing a bone-targeted form of TNALP was injected into the jugular vein of newborn Akp2(-/-) mice. We found that alkaline phosphatase activity in the plasma of treated Akp2(-/-) mice increased and remained at high levels throughout the life of the animals. The treated Akp2(-/-) mice survived for more than 10 months and demonstrated normal physical activity and a healthy appearance. Epileptic seizures were completely inhibited in the treated Akp2(-/-) mice, and X-ray examination of the skeleton showed that mineralization was significantly improved by the gene therapy. These results show that severe infantile HPP in TNALP knockout mice can be treated with a single injection of lentiviral vector during the neonatal period. |
