Murine Receptor Protein Tyrosine Phosphatase Sigma (mRPTP-sigma) was first cloned by us in 1994 (Wagner J, 1994). We subsequently generated the first RPTP-sigma knock-out mice and demonstrated that it presented with a defective neuroendocrine phenotype (Elchebly M, 1999).

PTPRS is highly expressed in the nervous system (Schaapveld RQ, 1998) (Figure 1), suggesting that its biological functions was also associated with neuronal development. After extensive studies of the PTPRS knockout mice, we found that nerve regeneration is indeed significantly enhanced in mice lacking PTPRS, in both peripheral and central nervous systems (PNS and CNS) (Thompson KM, 2003) (Sapieha PS, 2005) (Fry EJ, 2010).

In an exciting series of studies with our PTPRS gene-targeted mice, we and others demonstrated that PTPRS is the long-sought neuronal chondroitin sulphate proteoglycan (CSPG) receptor (Shen Y, 2009) (Fry EJ, 2010) (Figure 2). In adult mammalian CNS, neuroregeneration is tightly restricted by extracellular inhibitory factors such as CSPGs, which are produced by the glial scar. Together, these results identify PTPRS and its downstream signaling pathways as potential therapeutic targets for the promotion of axon growth following nerve injury.

Our current objectives are to understand PTPRS mechanisms of action at the molecular levels, to develop genetic and pharmacological means to inhibit RPTPs, and to test these potentially novel therapeutic agents in animal models of CNS injury.