Understanding the Delay in Onset of Paget's Disease of Bone
Abstract
One of the key questions in Paget s disease of bone (PDB) is the nature of the trigger for initiation of the disease. Inheritance of a predisposing mutation and childhood infection with Measles virus are important, but apparently insufficient to initiate the disease until a significant period of time has passed. Understanding what occurs in this intervening time period is the goal of this proposal. Our model involves the opposing action of two Measles virus genes. The MVV gene suppresses gene expression as part of the virus ability to promote persistent infection. The MVNP gene appears to activate gene expression to promote acute infection. In our model, when Measles virus infects a bone cell, the MVV gene creates a latent infection by suppressing gene expression in the cell. Then, a chance genetic event results in loss of the MVV gene and unmasking the MVNP gene, which then cooperates with the mutated SQSTM1 to initiate the exaggerated pattern of bone cell growth characteristic of PDB. We are presently testing this model. We have had difficulty cloning the MVV gene but propose a number of strategies to overcome this problem.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2014
- Accession Number
- ADA613442
Entities
People
- Marc F. Hansen
Organizations
- University of Connecticut Health Center