Astrocytosis and axonal proliferation in the hippocampus of S100b transgenic mice

Roger H Reeves, Jibin Yao, Michael R. Crowley, Suzanne Buck, Xiaofeng Zhang, Paul Yarowsky, John D. Gearhart, Dana C. Hilt

Research output: Contribution to journalArticle

Abstract

S100β is a calcium-binding protein that is expressed at high levels in brain primarily by astrocytes. Addition of the disulfide-bonded dimeric form of S100β to primary neuronal and glial cultures and established cell lines induces axonal extension and alterations in astrocyte proliferation and phenotype, but evidence that S100β exerts the same effects in vivo has not been presented. An 8.9-kb murine S100b genomic clone was used to produce two lines of transgenic mice in which S100β RNA is increased in a dose-related manner to 2-fold and 7-fold above normal. These lines show concomitant increased S100β protein throughout the brain. Expression in both lines is cell type- and tissue-appropriate, and expression levels are correlated with the transgene copy number, demonstrating that sequences necessary for normal regulation of the gene are included within the cloned segment. In the hippocampus of adult transgenic mice, Western blotting detects elevated levels of glial fibrillary acidic protein and several markers of axonal sprouting, including neurofilament L, phosphorylated epitopes of neurofilament H and M, and β-tubulin. Immunocytochemistry demonstrates alterations in astrocyte morphology and axonal sprouting, especially in the dentate gyrus. Thus, both astrocytosis and neurite proliferation occur in transgenic mice expressing elevated levels of S100β. These transgenic mice provide a useful model for studies of the role of S100β in glial-neuronal interactions in normal development and function of the brain and for analyzing the significance of elevated levels of S100β in Down syndrome and Alzheimer disease.

Original languageEnglish (US)
Pages (from-to)5359-5363
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number12
DOIs
StatePublished - Jun 7 1994

Fingerprint

Gliosis
Transgenic Mice
Hippocampus
Astrocytes
Intermediate Filaments
Neuroglia
Brain
Calcium-Binding Proteins
S100 Proteins
Glial Fibrillary Acidic Protein
Dentate Gyrus
Neurites
Tubulin
Down Syndrome
Transgenes
Disulfides
Epitopes
Alzheimer Disease
Clone Cells
Western Blotting

Keywords

  • chromosome 21
  • Down syndrome
  • neurodevelopment
  • neurotrophin

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Astrocytosis and axonal proliferation in the hippocampus of S100b transgenic mice. / Reeves, Roger H; Yao, Jibin; Crowley, Michael R.; Buck, Suzanne; Zhang, Xiaofeng; Yarowsky, Paul; Gearhart, John D.; Hilt, Dana C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 12, 07.06.1994, p. 5359-5363.

Research output: Contribution to journalArticle

Reeves, Roger H ; Yao, Jibin ; Crowley, Michael R. ; Buck, Suzanne ; Zhang, Xiaofeng ; Yarowsky, Paul ; Gearhart, John D. ; Hilt, Dana C. / Astrocytosis and axonal proliferation in the hippocampus of S100b transgenic mice. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 12. pp. 5359-5363.
@article{1c27caba942141679fe022b325365f80,
title = "Astrocytosis and axonal proliferation in the hippocampus of S100b transgenic mice",
abstract = "S100β is a calcium-binding protein that is expressed at high levels in brain primarily by astrocytes. Addition of the disulfide-bonded dimeric form of S100β to primary neuronal and glial cultures and established cell lines induces axonal extension and alterations in astrocyte proliferation and phenotype, but evidence that S100β exerts the same effects in vivo has not been presented. An 8.9-kb murine S100b genomic clone was used to produce two lines of transgenic mice in which S100β RNA is increased in a dose-related manner to 2-fold and 7-fold above normal. These lines show concomitant increased S100β protein throughout the brain. Expression in both lines is cell type- and tissue-appropriate, and expression levels are correlated with the transgene copy number, demonstrating that sequences necessary for normal regulation of the gene are included within the cloned segment. In the hippocampus of adult transgenic mice, Western blotting detects elevated levels of glial fibrillary acidic protein and several markers of axonal sprouting, including neurofilament L, phosphorylated epitopes of neurofilament H and M, and β-tubulin. Immunocytochemistry demonstrates alterations in astrocyte morphology and axonal sprouting, especially in the dentate gyrus. Thus, both astrocytosis and neurite proliferation occur in transgenic mice expressing elevated levels of S100β. These transgenic mice provide a useful model for studies of the role of S100β in glial-neuronal interactions in normal development and function of the brain and for analyzing the significance of elevated levels of S100β in Down syndrome and Alzheimer disease.",
keywords = "chromosome 21, Down syndrome, neurodevelopment, neurotrophin",
author = "Reeves, {Roger H} and Jibin Yao and Crowley, {Michael R.} and Suzanne Buck and Xiaofeng Zhang and Paul Yarowsky and Gearhart, {John D.} and Hilt, {Dana C.}",
year = "1994",
month = "6",
day = "7",
doi = "10.1073/pnas.91.12.5359",
language = "English (US)",
volume = "91",
pages = "5359--5363",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "12",

}

TY - JOUR

T1 - Astrocytosis and axonal proliferation in the hippocampus of S100b transgenic mice

AU - Reeves, Roger H

AU - Yao, Jibin

AU - Crowley, Michael R.

AU - Buck, Suzanne

AU - Zhang, Xiaofeng

AU - Yarowsky, Paul

AU - Gearhart, John D.

AU - Hilt, Dana C.

PY - 1994/6/7

Y1 - 1994/6/7

N2 - S100β is a calcium-binding protein that is expressed at high levels in brain primarily by astrocytes. Addition of the disulfide-bonded dimeric form of S100β to primary neuronal and glial cultures and established cell lines induces axonal extension and alterations in astrocyte proliferation and phenotype, but evidence that S100β exerts the same effects in vivo has not been presented. An 8.9-kb murine S100b genomic clone was used to produce two lines of transgenic mice in which S100β RNA is increased in a dose-related manner to 2-fold and 7-fold above normal. These lines show concomitant increased S100β protein throughout the brain. Expression in both lines is cell type- and tissue-appropriate, and expression levels are correlated with the transgene copy number, demonstrating that sequences necessary for normal regulation of the gene are included within the cloned segment. In the hippocampus of adult transgenic mice, Western blotting detects elevated levels of glial fibrillary acidic protein and several markers of axonal sprouting, including neurofilament L, phosphorylated epitopes of neurofilament H and M, and β-tubulin. Immunocytochemistry demonstrates alterations in astrocyte morphology and axonal sprouting, especially in the dentate gyrus. Thus, both astrocytosis and neurite proliferation occur in transgenic mice expressing elevated levels of S100β. These transgenic mice provide a useful model for studies of the role of S100β in glial-neuronal interactions in normal development and function of the brain and for analyzing the significance of elevated levels of S100β in Down syndrome and Alzheimer disease.

AB - S100β is a calcium-binding protein that is expressed at high levels in brain primarily by astrocytes. Addition of the disulfide-bonded dimeric form of S100β to primary neuronal and glial cultures and established cell lines induces axonal extension and alterations in astrocyte proliferation and phenotype, but evidence that S100β exerts the same effects in vivo has not been presented. An 8.9-kb murine S100b genomic clone was used to produce two lines of transgenic mice in which S100β RNA is increased in a dose-related manner to 2-fold and 7-fold above normal. These lines show concomitant increased S100β protein throughout the brain. Expression in both lines is cell type- and tissue-appropriate, and expression levels are correlated with the transgene copy number, demonstrating that sequences necessary for normal regulation of the gene are included within the cloned segment. In the hippocampus of adult transgenic mice, Western blotting detects elevated levels of glial fibrillary acidic protein and several markers of axonal sprouting, including neurofilament L, phosphorylated epitopes of neurofilament H and M, and β-tubulin. Immunocytochemistry demonstrates alterations in astrocyte morphology and axonal sprouting, especially in the dentate gyrus. Thus, both astrocytosis and neurite proliferation occur in transgenic mice expressing elevated levels of S100β. These transgenic mice provide a useful model for studies of the role of S100β in glial-neuronal interactions in normal development and function of the brain and for analyzing the significance of elevated levels of S100β in Down syndrome and Alzheimer disease.

KW - chromosome 21

KW - Down syndrome

KW - neurodevelopment

KW - neurotrophin

UR - http://www.scopus.com/inward/record.url?scp=0028337533&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028337533&partnerID=8YFLogxK

U2 - 10.1073/pnas.91.12.5359

DO - 10.1073/pnas.91.12.5359

M3 - Article

C2 - 8202493

AN - SCOPUS:0028337533

VL - 91

SP - 5359

EP - 5363

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 12

ER -