The creation of a mutant mouse replicating the genetic alteration found in LMS or Lehman Syndrome allowed us to test whether the skeletal phenotype of Notch3em1Ecan mice could be reversed by preventing the activation of NOTCH3 with anti-NOTCH3 antibodies targeting the NRR, the site required for the cleavage and activation of NOTCH3. Here, NOTCH3 is linked to lateral meningocele syndrome.