WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience MBF Stereo Investigator
 QUICK SEARCH:   [advanced]


     
-


HOME
  |  
SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, May 23, 2007, 27(21):5546-5558; doi:10.1523/JNEUROSCI.5540-06.2007

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Related articles in J. Neurosci.
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (6)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Meikle, L.
Right arrow Articles by Kwiatkowski, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Meikle, L.
Right arrow Articles by Kwiatkowski, D. J.

 Previous Article  |  Next Article 

Neurobiology of Disease
A Mouse Model of Tuberous Sclerosis: Neuronal Loss of Tsc1 Causes Dysplastic and Ectopic Neurons, Reduced Myelination, Seizure Activity, and Limited Survival

Lynsey Meikle,1 * Delia M. Talos,2 * Hiroaki Onda,1 Kristen Pollizzi,1 Alexander Rotenberg,2 Mustafa Sahin,2 Frances E. Jensen,2 and David J. Kwiatkowski1

1Division of Translational Medicine, Department of Medicine, Brigham and Women's Hospital and 2Department of Neurology, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115

Correspondence should be addressed to either of the following: David J. Kwiatkowski, One Blackfan Circle, 6-216, Division of Translational Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, Email: dk{at}rics.bwh.harvard.edu; or Frances E. Jensen, Enders 348, Neurology, Children's Hospital, Boston, 300 Longwood Avenue, Boston, MA 02115, E-mail: Email: frances.jensen{at}childrens.harvard.edu

Tuberous sclerosis (TSC) is a hamartoma syndrome caused by mutations in TSC1 or TSC2 in which cerebral cortical tubers and seizures are major clinical issues. We have engineered mice in which most cortical neurons lose Tsc1 expression during embryonic development. These Tsc1 mutant mice display several neurological abnormalities beginning at postnatal day 5 with subsequent failure to thrive and median survival of 35 d. The mice also display clinical and electrographic seizures both spontaneously and with physical stimulation, and some seizures end in a fatal tonic phase. Many cortical and hippocampal neurons are enlarged and/or dysplastic in the Tsc1 mutant mice, strongly express phospho-S6, and are ectopic in multiple sites in the cortex and hippocampus. There is a striking delay in myelination in the mutant mice, which appears to be caused by an inductive neuronal defect. This new TSC brain model replicates several features of human TSC brain lesions and implicates an important function of Tsc1/Tsc2 in neuronal development.

Key words: tuberous sclerosis; TSC1; mTOR; dysplastic neuron; ectopic neurons; seizures


Received Dec. 21, 2006; revised April 13, 2007; accepted April 14, 2007.

Correspondence should be addressed to either of the following: David J. Kwiatkowski, One Blackfan Circle, 6-216, Division of Translational Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, Email: dk{at}rics.bwh.harvard.edu; or Frances E. Jensen, Enders 348, Neurology, Children's Hospital, Boston, 300 Longwood Avenue, Boston, MA 02115, E-mail: Email: frances.jensen{at}childrens.harvard.edu


Related articles in J. Neurosci.:

This Week in The Journal

J. Neurosci. 2007 27: i. [Full Text]  



This article has been cited by other articles:


Home page
Genes Dev.Home page
J. Wildonger, L. Y. Jan, and Y. N. Jan
The Tsc1-Tsc2 complex influences neuronal polarity by modulating TORC1 activity and SAD levels
Genes & Dev., September 15, 2008; 22(18): 2447 - 2453.
[Abstract] [Full Text] [PDF]


Home page
Genes Dev.Home page
Y.-J. Choi, A. Di Nardo, I. Kramvis, L. Meikle, D. J. Kwiatkowski, M. Sahin, and X. He
Tuberous sclerosis complex proteins control axon formation
Genes & Dev., September 15, 2008; 22(18): 2485 - 2495.
[Abstract] [Full Text] [PDF]


Home page
J. Neurosci.Home page
L. Meikle, K. Pollizzi, A. Egnor, I. Kramvis, H. Lane, M. Sahin, and D. J. Kwiatkowski
Response of a Neuronal Model of Tuberous Sclerosis to Mammalian Target of Rapamycin (mTOR) Inhibitors: Effects on mTORC1 and Akt Signaling Lead to Improved Survival and Function
J. Neurosci., May 21, 2008; 28(21): 5422 - 5432.
[Abstract] [Full Text] [PDF]



-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help

-
Copyright 2008 by Society for Neuroscience ONLINE ISSN: 1529-2401
-