Inactivation of two mouse alkaline phosphatase genes and establishment of a model of infantile hypophosphatasia
Open Access
- 1 March 1997
- journal article
- research article
- Published by Wiley in Developmental Dynamics
- Vol. 208 (3), 432-446
- https://doi.org/10.1002/(sici)1097-0177(199703)208:3<432::aid-aja13>3.0.co;2-1
Abstract
We report the inactivation, via homologous recombination, of two of the three active mouse alkaline phosphatase genes, i.e., embryonic (EAP) and tissue nonspecific (TNAP). Whereas expression of the EAP isozyme was abolished in all tissues that express EAP developmentally (such as the preimplantation embryo, thymus, and testis), the EAP knock-out mice show no obvious phenotypic abnormalities. They reproduce normally and give birth to live offspring, indicating the nonessential role of EAP during embryonic development. Mice deficient in the TNAP gene mimic a severe form of hypophosphatasia. These TNAP −/− mice are growth impaired, develop epileptic seizures and apnea, and die before weaning. Examination of the tissues indicates abnormal bone mineralization and morphological changes in the osteoblasts, aberrant development of the lumbar nerve roots, disturbances in intestinal physiology, increased apoptosis in the thymus, and abnormal spleens. Our results indicate that, in the mouse, TNAP appears not to be essential for the initial events leading to bone mineral deposition but that TNAP seems to play a role in the maintenance of this process after birth. The other phenotypic manifestations may be a consequence of the lack of TNAP in the developing neural tube between stages E8.5 and E13.5 of embryogenesis. We hypothesize that the autonomic nervous system is compromised in these TNAP −/− mice. Dev. Dyn. 208:432–446, 1997.Keywords
This publication has 33 references indexed in Scilit:
- Vagal control of lymphocyte release from rat thymusJournal of the Autonomic Nervous System, 1994
- Phenotypically dissimilar hypophosphatasia in two sibshipsAmerican Journal of Medical Genetics, 1992
- Perinatal lethal hypophosphatasia; Clinical, radiologic and morphologic findingsPediatric Radiology, 1991
- Preimplantation Mouse Embryos Express a Heat-Stable Alkaline Phosphatase1Biology of Reproduction, 1989
- HypophosphatasiaMedicine, 1984
- Adult HypophosphatasiaMedicine, 1979
- Screening λgt Recombinant Clones by Hybridization to Single Plaques in SituScience, 1977
- AUTONOMIC NEUROPATHY OF ACUTE ONSETThe Lancet, 1974
- Serum alkaline phosphatase in hypophosphatasiaJCI Insight, 1971
- DEGENERATION OF THE AUTONOMIC NERVOUS SYSTEMThe Lancet, 1971