Selective expression of mutant huntingtin during development recapitulates characteristic features of Huntington's disease
Language: 
English
Abstract: 

Recent studies have identified impairments in neural induction and in striatal and cortical neurogenesis in Huntington's disease (HD) knock-in mouse models and associated embryonic stem cell lines. However, the potential role of these developmental alterations for HD pathogenesis and progression is currently unknown. To address this issue, we used BACHD:CAG-Cre(ERT2) mice, which carry mutant huntingtin (mHtt) modified to harbor a floxed exon 1 containing the pathogenic polyglutamine expansion (Q97). Upon tamoxifen administration at postnatal day 21, the floxed mHtt-exon1 was removed and mHtt expression was terminated (Q97(CRE)). These conditional mice displayed similar profiles of impairments to those mice expressing mHtt throughout life: (i) striatal neurodegeneration, (ii) early vulnerability to NMDA-mediated excitotoxicity, (iii) impairments in motor coordination, (iv) temporally distinct abnormalities in striatal electrophysiological activity, and (v) altered corticostriatal functional connectivity and plasticity. These findings strongly suggest that developmental aberrations may play important roles in HD pathogenesis and progression.

Author(s): 
Molero, Aldrin E.
Arteaga-Bracho, Eduardo E.
Chen, Christopher H.
Gulinello, Maria
Winchester, Michael L.
Pichamoorthy, Nandini
Gokhan, Solen
Khodakhah, Kamran
Mehler, Mark F.
Item Type: 
Journal Article
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America
Journal Abbreviation: 
Proc. Natl. Acad. Sci. U.S.A.
Publication Date: 
5/17/2016
Publication Year: 
2016
Pages: 
5736-5741
Volume: 
113
Issue: 
20
ISSN: 
1091-6490
DOI: 
10.1073/pnas.1603871113
Library Catalog: 
PubMed
Extra: 
PMID: 27140644 PMCID: PMC4878495

Turabian/Chicago Citation

Aldrin E. Molero, Eduardo E. Arteaga-Bracho, Christopher H. Chen, Maria Gulinello, Michael L. Winchester, Nandini Pichamoorthy, Solen Gokhan, Kamran Khodakhah and Mark F. Mehler. 5/17/2016. "Selective expression of mutant huntingtin during development recapitulates characteristic features of Huntington's disease." Proceedings of the National Academy of Sciences of the United States of America 113: 20: 5736-5741. 10.1073/pnas.1603871113.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1073/pnas.1603871113 | issn = 1091-6490 | volume = 113 | pages = 5736-5741 | last = Molero | first = Aldrin E. | coauthors = Arteaga-Bracho, Eduardo E., Chen, Christopher H., Gulinello, Maria, Winchester, Michael L., Pichamoorthy, Nandini, Gokhan, Solen, Khodakhah, Kamran, Mehler, Mark F. | title = Selective expression of mutant huntingtin during development recapitulates characteristic features of Huntington's disease | journal = Proceedings of the National Academy of Sciences of the United States of America | date = 5/17/2016 | pmid = | pmc = }} </ref>