ECTS2016 Poster Presentations Other diseases of bone and mineral metabolism (52 abstracts)
Chloride channel voltage-sensitive 7 (CLCN7) loss-of-function zebrafish as a genetic model of osteoclast-rich osteopetrosis
Katia Urso 1, , Joana Caetano-Lopes J 2, , Meera Sury 1 , Katrin Henke 2, , Antonios Aliprantis 1, , Matt Warman 2, , Jeff Duryea 1, , Matt Harris 2, & Julia Charles 1,
1Brigham and Womne’s Hospital, Boston, Massachusetts, USA; 2Harvard Medical School, Boston, Massachusetts, USA; 3Boston Children’s Hospital, Boston, Massachusetts, USA.
Osteoclasts are myeloid-derived cells that degrade bone through the localized production of acid and proteases. The catabolic action of osteoclasts is counterbalanced by formation of new matrix by osteoblasts. In mammals, bone resorption and formation are coupled through crosstalk between osteoclasts and osteoblasts. Zebrafish are emerging as a valuable model to study bone biology, but how closely zebrafish osteoclast function parallels that of higher vertebrates is unknown. To determine whether zebrafish osteoclasts utilize the same resorptive machinery as mammals, we generated a zebrafish lacking clcn7 using the CRISPR-Cas9 technique. In mammals, CLCN7 is required for chloride anion secretion and resorptive function in osteoclasts. Mutations of this protein result in lethal osteoclast-rich osteopetrosis in humans, and a similar phenotype is seen in CLCN7-deficient mice. We find that clcn7−/− zebrafish are viable and fertile. Osteoclast activity was determined by quantification of resorption pits in scales. Osteoclast activity is decreased in the mutant compared with wt fish, when the number and size of resorption pits on the scales are quantified. Micro-computed tomography of mutant fish reveals osteopetrosis and deformity of the vertebral arches, consistent with the observed resorption defects, and indicating that zebrafish also require CLCN7 for normal bone turnover and morphology in zebrafish. Future experiments will address whether osteoclast–osteoblast crosstalk occurs in zebrafish, since patients with CLCN7 mutations have increased osteoblast activity.
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Bone Abstracts
ISSN 2052-1219 (online)
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