Musculoskeletal Pathology Sustained Osteomalacia of Long Bones Despite Major Improvement in Other Hypophosphatasia- Related Mineral Deficits in Tissue Nonspecific

We have shown previously that the hypomineralization defects of the calvarium and vertebrae of tissue nonspe-cific alkaline phosphatase (TNAP)-deficient (Akp2/) hypophosphatasia mice are rescued by simultaneous deletion of the Enpp1 gene, which encodes nucleotide pyrophosphatase phosphodiesterase 1 (NPP1). Con-versely, the hyperossification in the vertebral apophy-ses typical of Enpp1/ mice is corrected in [Akp2/; Enpp1/] double-knockout mice. Here we have exam-ined the appendicular skeletons of Akp2/, Enpp1/, and [Akp2/;Enpp1/] mice to ascertain the degree of rescue afforded at these skeletal sites. Alizarin red and Alcian blue whole mount analysis of the skeletons from wild-type, Akp2/, and [Akp2/; Enpp1/] mice re-vealed that although calvarium and vertebrae of double