Induction of a NOTCH3 Lehman syndrome mutation in osteocytes causes osteopenia in male C57BL/6J mice.

ABSTRACT: Lateral Meningocele or Lehman Syndrome (LMS) is associated with NOTCH3 mutations causing deletions of the PEST domain and a gain-of-NOTCH3 function. We demonstrated that Notch3^em1Ecan mice harboring Notch3 mutations analogous to those found in LMS are osteopenic because of enhanced bone resorption. To determine the contribution of specific cell lineages to the phenotype, we created a conditional-by-inversion (Notch3^COIN) model termed Notch3^em2Ecan in which Cre recombination generates a Notch3^INV allele expressing a NOTCH3 mutant lacking the PEST domain. Germ line Notch3^COIN inversion caused osteopenia and phenocopied the Notch3^em1Ecan mutant, validating the model. To induce the mutation in osteocytes, smooth muscle and endot

SUBMITTER: Canalis E 

PROVIDER: S-EPMC10870228 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature