16 - Modelling Axial Defects Seen in CCMS in Mouse Model

Poster Board Number: 16
There are separate poster presentation times for odd and even posters.
Odd poster #s – first hour
Even poster #s – second hour

Co-authors:

Yanchen Dong - RI-MUHC; Sabrina Alam, Dr - RI-MUHC; Loydie Jerome-Majewska, Dr - Anatomy and Cell Biology, Human Genetics, Child Health and Human Development - RI-MUHC

Abstract Body : Cerebrocostomandibular Syndrome (CCMS) is a rare congenital disorder characterized by craniofacial and thoracic (axial) defects, namely micrognathia, cleft face/palate, posterior rib gaps, ectopic rib, a bell-shaped thoracic cage, and vertebral fusions. Thoracic defects seen in patients with CCMS lead to respiratory insufficiencies and, in 50% of cases, will ultimately lead to death in the first month of life. Patients carry pathogenic variants in the gene SNRPB which is expressed in both mesodermal and neural crest cell lineages. Neural crest cells contribute to most of the cartilage, bones, and connective tissue of the craniofacial and neck regions. While the mesoderm contributes to the development of the remaining parts of the craniofacial region along with the vertebrae and ribs. The mechanism through which SNRPB affects the proper differentiation of these cells in CCMS is unknown. My research objective is to test if axial defects seen in patients with SNRPB mutation can be phenocopied in mice. Using Mesp1-Cre and conditional Snrpb mutant mice, Snrpb was deleted in mesoderm cells. Histological analysis using haematoxylin and eosin staining to analyse the morphology and alician blue staining to analyse cartilage formation was completed.

Additionally, alician blue and alizarin red were used to analyse cartilage and bone formation respectively. Mesoderm-specific Snrpb mutant embryos are smaller than controls and the thoracic widths of these embryos are almost half the size of their wildtype littermates. These mutant embryos also have a bell-shaped thorax, smaller jaw, abnormal vertebrae body fusion and, in addition, the ribs of mutant embryos are wavy. Deletion of Snrpb using Mesp1-Cre phenocopy most of the axial defects found in CCMS patients in a mouse model. The levels and role of Snrpb and other genes important for axial development will be investigated in the future. This research is significant as it has the potential to understand the causation of this and other congenital diseases affecting axial development to reduce neonatal mortality and to identify therapeutic targets to rescue severe presentations observed.