Proteomic analysis of the function of DMPK, the myotonic dystrophy protein kinase

Myotonic Dystrophy type 1 (DM1), the most common form of adult-onset skeletal muscle dystrophy, is caused by expansion of a CTG repeat sequence embedded in the 3'UTR of a gene which encodes a serine threonine kinase, DMPK. The precise mechanism by which CTG repeat expansion causes the complex pathology of DM1 is under active investigation. Repeat expansion leads to a failure of transport of DMPK mRNA from nucleus to cytoplasm indicating that reduction in DMPK expression levels is at least one major consequence of repeat expansion. Mouse models suggest that haploinsufficiency of DMPK accounts for at least a portion of the symptoms of DM1. DMPK -/- mice exhibit a progressive muscle myopathy similar to that seen in DM1, and both DMPK -/- and DMPK +/- mice reiterate cardiac conduction abnormalities characteristic of DM1 patients. However, the in vivo role of DMPK, the identity and nature of its substrate(s) and the biological pathway(s) within which it functions remain to be elucidated. To determine the in vivo function of DMPK I have taken a proteomics-based approach that utilizes 2-dimensional SDS-PAGE and mass spectrometry to compare directly heart proteins of wild-type and DMPK -/- mice in order to identify proteins that are altered in the absence of DMPK.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2001

Author dc:creator

• Luciano, Brenda Sierra, 1965-

Advisor dc:contributor.advisor

• David Evan Housman.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/8207

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/8207