A mouse model of Jansen's metaphyseal chondrodysplasia for investigating disease mechanisms and candidate therapeutics.

ABSTRACT: Jansen's metaphyseal chondrodysplasia (JMC) is a rare disorder caused by activating mutations in the parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor (PTH1R). Patients exhibit short stature, dysmorphic bones, and severe growth plate abnormalities, as well as hypercalcemia, hypercalciuria, hypophosphatemia, and reduced plasma PTH levels. Humanized PTH1R (hPTH1R) mice expressing the H223R-hPTH1R JMC mutation die early without breeding. We therefore generated and characterized a stable mouse line expressing the T410R-hPTH1R allele, which confers a milder disease phenotype in patients. Mutant mice show near-normal longevity and reproductive capacity yet exhibit a profound skeletal phenotype characteristic of the disease. The long bones of T410R mice are markedly misshapen and hav

SUBMITTER: Hoppner J 

PROVIDER: S-EPMC12167993 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature