5.5.1. GACI Mice

The first evidence of a link between defective *Enpp1* expression and abnormal mineralization was first demonstrated in 'tiptoe walking' (*ttw*/*ttw*) mice [118]. The various *Enpp1* deficient mouse models that exist present similar characteristics. The animals with a naturally occurring mutation (*ttw*/*ttw*) carry a homozygous nonsense variant in the *Enpp1* coding sequence [118], whereas another mouse model harbors a missense mutation [119]. The phenotype of these mice includes progressive ankylosing intervertebral and peripheral joint hyperostosis, as well as spontaneous arterial and articular cartilage calcification and increased vertebral cortical bone formation. Low plasma PPi and PXE-like calcification are fundamental characteristics of these mice [119,120]. These animals also have abnormal ossification, cardiovascular pathologies and altered glucose homeostasis and diabetes [121,122].
