Importantly, special care should be taken to schedule radiation therapy appropriately, as our data show that the use of vasodilators result in increased hypoxia, which could decrease radiotherapy efficacy in patients that demonstrate a “steal” effect. Generalized arterial calcification of infancy is a severe ectopic mineralization disorder affecting primarily the arterial blood vessels in humans. The disease is often diagnosed by prenatal ultrasound, and the affected individuals in most cases die within the first year of life from cardiovascular complications. GACI is inherited in an autosomal recessive fashion, and most cases are due to mutations in the ENPP1 gene, which encodes ectonucleotide pyrophosphatase/ phosphodiesterase 1, an enzyme that hydrolyses ATP to AMP and inorganic pyrophosphate. Under physiological conditions, PPi serves as a powerful anti-mineralization factor, and with reduced ENPP1 activity in GACI, the ratio of inorganic phosphate to PPi increases creating a promineralization environment and allowing ectopic tissue mineralization to ensue. There is currently no effective treatment for GACI. A number of mouse models recapitulating the clinical features of human diseases with vascular mineralization have been described. One of them, the asj mouse, was recently identified as a result of ENU treatment in The Jackson Laboratory Neuromutagenesis Program. These mice were originally noted to demonstrate a stiff posture, abnormalities in the front legs, and a progressive, SU5416 ageassociated stiffening of the joints.. Collectively, under normal physiologic conditions, there is a complex pro-mineralization/anti-mineralization network that is required to maintain the normal homeostatic ratio of PPi/Pi. Mutations in many of the genes controlling this ratio have been shown to result in ectopic mineralization of the soft connective tissues, particularly in the skin and the arterial blood vessels. For example, mutations in the ENPP1 gene result in GACI, mutations in the ABCC6 gene underlie PXE, and patients with mutations in the NT5E gene, which encodes CD73, develop arterial calcification due to CD73 deficiency. A number of animal models, particularly targeted and spontaneous mutant mice, have been extremely helpful in providing pathomechanistic information on ectopic mineralization in human diseases. In this study, we describe a novel mutant mouse, asj-2J, which was identified in the colony breeding program of The Jackson Laboratory. This mouse was noted to have extensive mineralization of the dermal sheath of vibrissae as well as arterial blood vessels, and the mice developed a phenotypic gait due to periarticular mineral deposits. The mineralization phenotype could be significantly accelerated by placing the mice on “acceleration diet”, enriched in phosphate and low in magnesium. The phenotypic similarity of these mutant mice with a previously described asj mouse prompted us to test the hypothesis that asj-2J mice were allelic, and complementation studies supported the notion that both mice had mutations in the same gene, Enpp1. Previous studies have demonstrated that asj mice harbor a homozygous missense mutation V246D.