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PMID: 11157067 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Two distal downstream enhancers direct expression of the human apolipoprotein E gene to astrocytes in the brain.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 21 ·No. 3 ·2001-02-01 ·Pages 812-22

Grehan S, Tse E, Taylor JM

Abstract

Two distal downstream enhancers controlling astrocyte expression of the human apolipoprotein E (apoE) gene in the brain were identified by analysis of transgenic mice generated with various constructs of the apoE/C-I/C-IV/C-II gene cluster. In wild-type mice, the highest overall levels of apoE mRNA were found in astrocytes in the glomerular layer of olfactory bulbs and in Bergmann glia in the cerebellum. This pattern of expression was reproduced in transgenic mice expressing the entire human apoE gene cluster and also in transgenic mice expressing specific enhancer segments within the cluster. Expression of the human apoE transgene at these sites was specified by two enhancer domains: one enhancer is located 3.3 kb downstream of the apoE gene, and a duplication of this sequence is located 15 kb downstream of the apoE gene. Astrocyte enhancer activity was contained within 620 and 619 bp segments of these domains that show subtle differences in regional expression. In the absence of these distal enhancers, the apoE gene was not expressed in astrocytes. The relatively high levels of apoE expression at specific sites in the olfactory bulb and cerebellum suggest the presence of unique regulatory signals at these locations that may reflect common cellular properties and apoE gene functions. The localization of the two astrocytic enhancers reveals an unexpected complexity in the control of apoE production that is essential to understanding apoE function in the brain.

MeSH Terms
Animals Apolipoproteins E/genetics,metabolism Astrocytes/cytology,metabolism Brain/cytology,metabolism Cerebellum/cytology,metabolism Enhancer Elements, Genetic/physiology Gene Expression Regulation/physiology Genes, Reporter Humans Immunohistochemistry Mice Mice, Transgenic Multigene Family/genetics Olfactory Bulb/cytology,metabolism Organ Specificity Promoter Regions, Genetic/physiology RNA, Messenger/metabolism Transgenes/genetics
Chemicals
Apolipoproteins E RNA, Messenger
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Grehan S
Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141-9100, USA.
Tse E
Taylor J M
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2001-02-01
Pages
812-22
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6762321
Subset
IM
Grants
NHLBI NIH HHS · R01 HL037063 · United States
NHLBI NIH HHS · HL37063 · United States
External Links
PubMed source PMC Full Text View journal details
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