René St-Arnaud

René St-Arnaud

René St-Arnaud


Senior Investigator at the Canadian Shriners Hospital for Children

Professor of Medicine, Surgery, and Human Genetics, McGill University

Area of Research: 

  • control of gene expression in bone cells
  • vitamin D metabolism

Contact Information:

rst-arnaud [at] (Email)

Recent Publications:


Summary of Research:

a) Vitamin D synthesis in bone: molecular genetic analysis

The enzyme 25-hydroxyvitamin D-1α-hydroxylase (1α-OHase) converts 25(OH)D to 1,25(OH)2D, the active form of vitamin D. We have engineered mutant strains of mice that do not express the 1α-OHase gene in chondrocytes. In parallel, we plan to engineer strains of mice overexpressing a 1α-OHase transgene in chondrocytes. Contrasting the phenotype of the transgenic animals to that of the knock-out animals should help elucidate the role of local production of the hormonal form of vitamin D during cartilage formation, maturation, and growth. The 25-hydroxyvitamin D-24-hydroxylase enzyme (24-OHase) converts 25(OH)D to 24,25(OH)2D, a metabolite that may be important during fracture repair. We have engineered a strain of mice deficient for the 24-OHase enzyme. Fracture repair will be analyzed in the 24-OHase-deficient mice using the distraction osteogenesis mouse model. These studies will address key aspects of vitamin D biology and lead to the development of new animal models of disease involving the vitamin D endocrine system.

b) Gene expression in bone cells

We have cloned the transcriptional coactivator, αNAC, that is expressed in bone during development. We have shown that the Integrin Linked Kinase (ILK) can efficiently phosphorylate αNAC. We have identified a novel factor interacting with αNAC that we termed FIAT, for Factor Inhibiting ATF4-mediated Transcription. Our results show that FIAT inhibits ATF4 activity and osteocalcin gene transcription. We are currently generating strains of mice deficient for αNAC, FIAT, and ILK. Our recent results show that chondrocyte-specific ablation of ILK leads to chondrodysplasia while its inactivation in osteoclasts leads to mild osteopetrosis. FIAT overexpression in osteoblasts reduces bone mass in vivo. Our research will further our knowledge of the molecular mechanisms regulating bone cell-specific gene expression and allow to develop animal models of bone diseases involving the genes that we have cloned.




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