Grant: Project Grant
Research Institute of the McGill University Health Centre
$612,000.00
Understanding how a novel mutation in matrix Gla protein causes skeletal anomalies
FY 2023-24
Summary
Matrix Gla protein (MGP) acts as a potent inhibitor of soft tissue calcification in vascular and cartilaginous tissues. The complete loss of this protein in humans leads to calcification of almost all cartilage tissues, and some vascular tissues. Interestingly, a new genetic mutation recently found in human MGP gene results in an abnormal protein which causes a distinct set of bone and joint deformities that are not seen in patients with the complete loss of MGP proteins. We have generated a new mouse model recapitulating the novel human mutation and observed similar skeletal abnormalities as seen in the individuals carrying this mutation. In the current study, we will use this mouse model to characterize the skeletal traits, understand the mechanism that causes the skeletal problems and investigate the efficacy of a potential treatment strategy. This work may open up new avenues to treat the patients with similar skeletal deformities.
Department
Program
Project Grant
Location
Quebec, Canada
Type
Grant
Source
CIHR Funding Decisions Database
As published
Id
489768
Name
Murshed Monzur
Region
Québec
Country
Canada
Orgtype
Institution Paid; Research Institution
Instname2
Musculoskeletal Health and Arthritis
Theme2
Biomedical
Prcname2
Clinical Investigation - B: Arthritis, Bone, Skin and Cartilage
Projecttitle
Understanding how a novel mutation in matrix Gla protein causes skeletal anomalies
Programtype2
Operating Grants
Orgnameinp2
Research Institute of the McGill University Health Centre
Cihramount2
$612,000
Cihrequipment2
$0
Programname2
Project Grant
Keyworddelim
Apoptosis; Bone Remodeling; Chondrogenesis; Endoplasmic Reticulum Stress; Histomorphometry; Matrix Gla Protein; Micro-Ct; Mouse Models; Skeletal Development; Skeletal Dysplasia
Abstract
Matrix Gla protein (MGP) acts as a potent inhibitor of soft tissue calcification in vascular and cartilaginous tissues. The complete loss of this protein in humans leads to calcification of almost all cartilage tissues, and some vascular tissues. Interestingly, a new genetic mutation recently found in human MGP gene results in an abnormal protein which causes a distinct set of bone and joint deformities that are not seen in patients with the complete loss of MGP proteins. We have generated a new mouse model recapitulating the novel human mutation and observed similar skeletal abnormalities as seen in the individuals carrying this mutation. In the current study, we will use this mouse model to characterize the skeletal traits, understand the mechanism that causes the skeletal problems and investigate the efficacy of a potential treatment strategy. This work may open up new avenues to treat the patients with similar skeletal deformities.
Competitiondate
202309
Approvedterm2
5 yrs 0 mth
Pinamesdelim
Murshed, Monzur
Approvedterm
5 ans 0 mois
Cihrcontribution2
~ $612,000~ $0~
