Astrocyte-specific TSC1 conditional knockout mice exhibit abnormal neuronal organization and seizures.

Abstract:

:Persons affected with tuberous sclerosis complex (TSC) develop a wide range of neurological abnormalities including aberrant neuronal migration and seizures. In an effort to model TSC-associated central nervous system abnormalities in mice, we generated two independent lines of astrocyte-specific Tsc1 conditional knockout mice by using the Cre-LoxP system. Astrocyte-specific Tsc1-null mice exhibit electroencephalographically proven seizures after the first month of age and begin to die at 3 to 4 months. Tsc1-null mice show significant increases in astrocyte numbers throughout the brain by 3 weeks of age and abnormal neuronal organization in the hippocampus between 3 and 5 weeks. Moreover, cultured Tsc1-null astrocytes behave similar to wild-type astrocytes during log phase growth but demonstrate increased saturation density associated with reduced p27(Kip1) expression. Collectively, our results demonstrate that astrocyte-specific disruption of Tsc1 in mice provides a context-dependent growth advantage for astrocytes that results in abnormalities in neuronal organization and epilepsy.

journal_name

Ann Neurol

journal_title

Annals of neurology

authors

Uhlmann EJ,Wong M,Baldwin RL,Bajenaru ML,Onda H,Kwiatkowski DJ,Yamada K,Gutmann DH

doi

10.1002/ana.10283

keywords:

subject

Has Abstract

pub_date

2002-09-01 00:00:00

pages

285-96

issue

3

eissn

0364-5134

issn

1531-8249

journal_volume

52

pub_type

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