The lateral meningocele syndrome mutation causes marked osteopenia in mice.

ABSTRACT: Lateral meningocele syndrome (LMS) is a rare genetic disorder characterized by neurological complications and osteoporosis. LMS is associated with mutations in exon 33 of NOTCH3 leading to a truncated protein lacking sequences for NOTCH3 degradation and presumably causing NOTCH3 gain of function. To create a mouse model reproducing human LMS-associated mutations, we utilized CRISPR/Cas9 to introduce a tandem termination codon at bases 6691-6696 (ACCAAG→TAATGA) and verified this mutation (Notch3^tm1.1Ecan ) by DNA sequencing of F1 mice. One-month-old male and female heterozygous Notch3^tm1.1Ecan mice had cancellous and cortical bone osteopenia but exhibited no obvious neurological alterations, and histopathology of multiple organs revealed no abnorma

SUBMITTER: Canalis E 

PROVIDER: S-EPMC6130932 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature