Generation of an immunodeficient mouse model of tcirg1-deficient autosomal recessive osteopetrosis.

ABSTRACT:

Background

Autosomal recessive osteopetrosis is a rare skeletal disorder with increased bone density due to a failure in osteoclast bone resorption. In most cases, the defect is cell-autonomous, and >50% of patients bear mutations in the TCIRG1 gene, encoding for a subunit of the vacuolar proton pump essential for osteoclast resorptive activity. The only cure is hematopoietic stem cell transplantation, which corrects the bone pathology by allowing the formation of donor-derived functional osteoclasts. Therapeutic approaches using patient-derived cells corrected ex vivo through viral transduction or gene editing can be considered, but to date functional rescue cannot be demonstrated in vivo because a relevant animal model for xenotransplant is missing.

Method

SUBMITTER: Palagano E 

PROVIDER: S-EPMC6953598 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature