Parkinson's disease-like neuromuscular defects occur in prenyl diphosphate synthase subunit 2 (Pdss2) mutant mice

详细信息	查看全文 | 推荐本文 |

• 作者：Carly G.K. Ziegler^a ; ^b ; Min Peng^a ; Marni J. Falk^c ; Erzsebet Polyak^c ; Elpida Tsika^d ; ^e ; Harry Ischiropoulos^b ; ^d ; Dana Bakalar^b ; Julie A. Blendy^b ; David L. Gasser^a ; ^{gasserd@mail.med.upenn.edu}
• 关键词：Parkinson's disease ; Coenzyme Q ; Dopaminergic neurons
• 刊名：Mitochondrion
• 出版年：2012
• 期刊代码：39_15677249
• 类别：neu
• 出版时间：March, 2012
• 卷：12
• 期：2
• 页码：248-257
• 文件大小：1899 K

摘要

The Pdss2 gene product is needed for the isoprenylation of benzoquinone to generate coenzyme Q (CoQ). A fatal kidney disease occurs in mice that are homozygous for a missense mutation in Pdss2, which can be recapitulated in conditional Pdss2 knockouts targeted to glomerular podocytes. We now report that homozygous missense mutants also demonstrate significant neuromuscular deficits, as validated by behavioral and coordination assays, and these deficits are recapitulated in conditional Pdss2 knockouts targeted to dopaminergic neurons. Both conditional knockout and missense mutant mice demonstrate deficiencies in tyrosine hydroxylase-positive neurons in the substantia nigra, implicating a pathology similar to sporadic Parkinson's disease (PD).