Antisense oligonucleotides targeting Notch2 ameliorate the osteopenic phenotype in a mouse model of Hajdu-Cheney syndrome.

ABSTRACT: Notch receptors play critical roles in cell-fate decisions and in the regulation of skeletal development and bone remodeling. Gain-of-function NOTCH2 mutations can cause Hajdu-Cheney syndrome, an untreatable disease characterized by osteoporosis and fractures, craniofacial developmental abnormalities, and acro-osteolysis. We have previously created a mouse model harboring a point 6955C→T mutation in the Notch2 locus upstream of the PEST domain, and we termed this model Notch2^tm1.1Ecan Heterozygous Notch2^tm1.1Ecan mutant mice exhibit severe cancellous and cortical bone osteopenia due to increased bone resorption. In this work, we demonstrate that the subcutaneous administration of Notch2 antisense oligonucleotides (ASO) down-regulates Not

SUBMITTER: Canalis E 

PROVIDER: S-EPMC7086019 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature