| | |  | | | | Record from Web of Science® | | | | | | |
| CAG EXPANSION AFFECTS THE EXPRESSION OF MUTANT HUNTINGTIN IN THE HUNTINGTONS-DISEASE BRAIN |
|
|
| Author(s): ARONIN N, CHASE K, YOUNG C, SAPP E, SCHWARZ C, MATTA N, KORNREICH R, LANDWEHRMEYER B, BIRD E, BEAL MF, VONSATTEL JP, SMITH T, CARRAWAY R, BOYCE FM, YOUNG AB, PENNEY JB, DIFIGLIA M |
| Source: NEURON Volume: 15 Issue: 5 Pages: 1193-1201 Published: NOV 1995 |
| Times Cited: 97 References: 33 |
| Abstract: A trinucleotide repeat (GAG) expansion in the huntingtin gene causes Huntington's disease (HD). In brain tissue from HD heterozygotes with adult onset and more clinically severe juvenile onset, where the largest expansions occur, a mutant protein of equivalent intensity to wild-type huntingtin was detected in cortical synaptosomes, indicating that a mutant species is synthesized and transported with the normal protein to nerve endings. The increased size of mutant huntingtin relative to the wild type was highly correlated with CAG repeat expansion, thereby linking an altered electrophoretic mobility of the mutant protein to its abnormal function. Mutant huntingtin appeared in gray and white matter with no difference in expression in affected regions. The mutant protein was broader than the wild type and in 6 of 11 juvenile cases resolved as a complex of bands, consistent with evidence at the DNA level for somatic mosaicism. Thus, HD pathogenesis results from a gain of function by an aberrant protein that is widely expressed in brain and is harmful only to some neurons. |
| Document Type: Article |
| Language: English |
Addresses:
1. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT NEUROL, BOSTON, MA 02114 USA
2. UNIV MASSACHUSETTS, MED CTR, DEPT PHYSIOL, WORCESTER, MA 01655 USA
3. UNIV MASSACHUSETTS, MED CTR, DEPT PATHOL, WORCESTER, MA 01655 USA
4. UNIV MASSACHUSETTS, MED CTR, DEPT MED, WORCESTER, MA 01655 USA
5. UNIV MASSACHUSETTS, MED CTR, DEPT CELL BIOL, WORCESTER, MA 01655 USA
6. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PATHOL, BOSTON, MA 02114 USA
7. DIANON SYST INC, STAMFORD, CT 06497 USA |
| Publisher: CELL PRESS, 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 |
| Subject Category: Neurosciences |
| IDS Number: TF887 |
| ISSN: 0896-6273 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |