ENPP1 enzyme replacement therapy improves ectopic calcification but does not rescue skeletal phenotype in a mouse model for craniometaphyseal dysplasia.

ABSTRACT: Craniometaphyseal dysplasia (CMD) is a rare genetic bone disorder, characterized by progressive thickening of craniofacial bones and flared metaphyses of long bones. Craniofacial hyperostosis leads to the obstruction of neural foramina and neurological symptoms such as facial palsy, blindness, deafness, or severe headache. Mutations in ANKH (mouse ortholog ANK), a transporter of small molecules such as citrate and ATP, are responsible for autosomal dominant CMD. Knock-in (KI) mice carrying an ANK_F377del mutation (Ank^KI/KI ) replicate many features of human CMD. Pyrophosphate (PPi) levels in plasma are significantly reduced in Ank^KI/KI mice. PPi is a potent inhibitor of mineralization. To examine the extent to which restoration of

SUBMITTER: Reichenberger EJ 

PROVIDER: S-EPMC11334334 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature