[HTML][HTML] Sustained Notch2 signaling in osteoblasts, but not in osteoclasts, is linked to osteopenia in a mouse model of Hajdu-Cheney syndrome
Individuals with Hajdu-Cheney syndrome (HCS) present with osteoporosis, and HCS is
associated with NOTCH2 mutations causing deletions of the proline-, glutamic acid-, serine-,
and threonine-rich (PEST) domain that are predicted to enhance NOTCH2 stability and
cause gain-of-function. Previously, we demonstrated that mice harboring Notch2 mutations
analogous to those in HCS (Notch2HCS) are severely osteopenic because of enhanced
bone resorption. We attributed this phenotype to osteoclastic sensitization to the receptor …
associated with NOTCH2 mutations causing deletions of the proline-, glutamic acid-, serine-,
and threonine-rich (PEST) domain that are predicted to enhance NOTCH2 stability and
cause gain-of-function. Previously, we demonstrated that mice harboring Notch2 mutations
analogous to those in HCS (Notch2HCS) are severely osteopenic because of enhanced
bone resorption. We attributed this phenotype to osteoclastic sensitization to the receptor …