Generation of mice with glial cell dysfunction

Kenji Tanaka, Ung Lee Hae, Kazuhiro Ikenaka

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

To examine astrocytic function, we have developed model mice harboring astrocyte-specific disease causal gene and tried to examine astrocytic function in vivo. Alexander disease, megalencephalic leukodystrophy with subcortical cysts (MLC), and autistic spectrum disorder with neuroligin 3/4 mutations are known to be astrocyte-specific disease so far. First of all, we have established Alexander disease model mouse. Alexander disease is caused by coding mutation in glial fibrillary acidic protein (GFAP) and mutant GFAP forms inclusion bodies, called Rosenthal fibers, in astrocytes. Its pathophysiology is still unknown. We generated transgenic mice that express human GFAP R239H mutant under the control of mouse GFAP promoter. Lines with single copy exhibited weak human GFAP expression in astrocytes that did not produce aggregates despite the existence of mutation, whereas lines with multi copies exhibited strong expression and the formation of aggregates, starting at P14. The line with aggregates showed higher sensitivity to kainate than the line without them, whose sensitivity was not different from the wild type mouse, suggesting that the presence of GFAP aggregates but not the presence of mutant GFAP altered the sensitivity. Changes in several electrophysiological parameters, including facilitation of LTP, were also observed in this model mouse. We believe that this transgenic line is a useful tool to study astrocytic function in vivo.

Original languageEnglish
Pages (from-to)747-753
Number of pages7
JournalBrain and Nerve
Volume59
Issue number7
Publication statusPublished - 2007 Jul
Externally publishedYes

Fingerprint

Glial Fibrillary Acidic Protein
Neuroglia
Alexander Disease
Astrocytes
Mutant Proteins
Mutation
Kainic Acid
Inclusion Bodies
Autistic Disorder
Transgenic Mice
Cysts
Genes

Keywords

  • Alexander disease
  • Astrocyte
  • GFAP
  • Mlcl
  • Neuroligin 3

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Tanaka, K., Hae, U. L., & Ikenaka, K. (2007). Generation of mice with glial cell dysfunction. Brain and Nerve, 59(7), 747-753.

Generation of mice with glial cell dysfunction. / Tanaka, Kenji; Hae, Ung Lee; Ikenaka, Kazuhiro.

In: Brain and Nerve, Vol. 59, No. 7, 07.2007, p. 747-753.

Research output: Contribution to journalArticle

Tanaka, K, Hae, UL & Ikenaka, K 2007, 'Generation of mice with glial cell dysfunction', Brain and Nerve, vol. 59, no. 7, pp. 747-753.
Tanaka K, Hae UL, Ikenaka K. Generation of mice with glial cell dysfunction. Brain and Nerve. 2007 Jul;59(7):747-753.
Tanaka, Kenji ; Hae, Ung Lee ; Ikenaka, Kazuhiro. / Generation of mice with glial cell dysfunction. In: Brain and Nerve. 2007 ; Vol. 59, No. 7. pp. 747-753.
@article{174d0834079d479f8bac8de8c7f267d6,
title = "Generation of mice with glial cell dysfunction",
abstract = "To examine astrocytic function, we have developed model mice harboring astrocyte-specific disease causal gene and tried to examine astrocytic function in vivo. Alexander disease, megalencephalic leukodystrophy with subcortical cysts (MLC), and autistic spectrum disorder with neuroligin 3/4 mutations are known to be astrocyte-specific disease so far. First of all, we have established Alexander disease model mouse. Alexander disease is caused by coding mutation in glial fibrillary acidic protein (GFAP) and mutant GFAP forms inclusion bodies, called Rosenthal fibers, in astrocytes. Its pathophysiology is still unknown. We generated transgenic mice that express human GFAP R239H mutant under the control of mouse GFAP promoter. Lines with single copy exhibited weak human GFAP expression in astrocytes that did not produce aggregates despite the existence of mutation, whereas lines with multi copies exhibited strong expression and the formation of aggregates, starting at P14. The line with aggregates showed higher sensitivity to kainate than the line without them, whose sensitivity was not different from the wild type mouse, suggesting that the presence of GFAP aggregates but not the presence of mutant GFAP altered the sensitivity. Changes in several electrophysiological parameters, including facilitation of LTP, were also observed in this model mouse. We believe that this transgenic line is a useful tool to study astrocytic function in vivo.",
keywords = "Alexander disease, Astrocyte, GFAP, Mlcl, Neuroligin 3",
author = "Kenji Tanaka and Hae, {Ung Lee} and Kazuhiro Ikenaka",
year = "2007",
month = "7",
language = "English",
volume = "59",
pages = "747--753",
journal = "Brain and Nerve",
issn = "0006-8969",
publisher = "Igaku-Shoin Ltd",
number = "7",

}

TY - JOUR

T1 - Generation of mice with glial cell dysfunction

AU - Tanaka, Kenji

AU - Hae, Ung Lee

AU - Ikenaka, Kazuhiro

PY - 2007/7

Y1 - 2007/7

N2 - To examine astrocytic function, we have developed model mice harboring astrocyte-specific disease causal gene and tried to examine astrocytic function in vivo. Alexander disease, megalencephalic leukodystrophy with subcortical cysts (MLC), and autistic spectrum disorder with neuroligin 3/4 mutations are known to be astrocyte-specific disease so far. First of all, we have established Alexander disease model mouse. Alexander disease is caused by coding mutation in glial fibrillary acidic protein (GFAP) and mutant GFAP forms inclusion bodies, called Rosenthal fibers, in astrocytes. Its pathophysiology is still unknown. We generated transgenic mice that express human GFAP R239H mutant under the control of mouse GFAP promoter. Lines with single copy exhibited weak human GFAP expression in astrocytes that did not produce aggregates despite the existence of mutation, whereas lines with multi copies exhibited strong expression and the formation of aggregates, starting at P14. The line with aggregates showed higher sensitivity to kainate than the line without them, whose sensitivity was not different from the wild type mouse, suggesting that the presence of GFAP aggregates but not the presence of mutant GFAP altered the sensitivity. Changes in several electrophysiological parameters, including facilitation of LTP, were also observed in this model mouse. We believe that this transgenic line is a useful tool to study astrocytic function in vivo.

AB - To examine astrocytic function, we have developed model mice harboring astrocyte-specific disease causal gene and tried to examine astrocytic function in vivo. Alexander disease, megalencephalic leukodystrophy with subcortical cysts (MLC), and autistic spectrum disorder with neuroligin 3/4 mutations are known to be astrocyte-specific disease so far. First of all, we have established Alexander disease model mouse. Alexander disease is caused by coding mutation in glial fibrillary acidic protein (GFAP) and mutant GFAP forms inclusion bodies, called Rosenthal fibers, in astrocytes. Its pathophysiology is still unknown. We generated transgenic mice that express human GFAP R239H mutant under the control of mouse GFAP promoter. Lines with single copy exhibited weak human GFAP expression in astrocytes that did not produce aggregates despite the existence of mutation, whereas lines with multi copies exhibited strong expression and the formation of aggregates, starting at P14. The line with aggregates showed higher sensitivity to kainate than the line without them, whose sensitivity was not different from the wild type mouse, suggesting that the presence of GFAP aggregates but not the presence of mutant GFAP altered the sensitivity. Changes in several electrophysiological parameters, including facilitation of LTP, were also observed in this model mouse. We believe that this transgenic line is a useful tool to study astrocytic function in vivo.

KW - Alexander disease

KW - Astrocyte

KW - GFAP

KW - Mlcl

KW - Neuroligin 3

UR - http://www.scopus.com/inward/record.url?scp=34447650626&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34447650626&partnerID=8YFLogxK

M3 - Article

C2 - 17663146

AN - SCOPUS:34447650626

VL - 59

SP - 747

EP - 753

JO - Brain and Nerve

JF - Brain and Nerve

SN - 0006-8969

IS - 7

ER -