Cystatin B-deficient mice have increased expression of apoptosis and glial activation genes

Lieuallen, Kimberly; Pennacchio, Len A; Park, Morgan; Myers, Richard M; Lennon, Gregory G

doi:10.1093/hmg/10.18.1867

Title: Cystatin B-deficient mice have increased expression of apoptosis and glial activation genes

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Abstract

Loss-of-function mutations in the cystatin B (Cstb) gene cause a neurological disorder known as Unverricht Lundborg disease (EPM1) in human patients. Mice that lack Cstb provide a mammalian model for EPM1 by displaying progressive ataxia and myoclonic seizures. We analyzed RNAs from brains of Cstb-deficient mice by using modified differential display, oligonucleotide microarray hybridization and quantitative reverse transcriptase polymerase chain reaction to examine the molecular consequences of the lack of Cstb. We identified seven genes that have consistently increased transcript levels in neurological tissues from the knockout mice. These genes are cathepsin S, C1q B-chain of complement (C1qB), beta-2-microglobulin, glial fibrillary acidic protein (Gfap), apolipoprotein D, fibronectin 1 and metallothionein II, which are expected to be involved in increased proteolysis, apoptosis and glial activation. The molecular changes in Cstb-deficient mice are consistent with the pathology found in the mouse model and may provide clues towards the identification of therapeutic points of intervention for EPM1 patients.

Authors:: Lieuallen, Kimberly; Pennacchio, Len A; Park, Morgan; Myers, Richard M; Lennon, Gregory G

Publication Date:: Thu Jul 05 00:00:00 EDT 2001

Research Org.:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Org.:: USDOE Director. Office of Science. Office of Biological and Environmental Research, Oak Ridge Institute for Science and Education; American Epilepsy Society Research Fellowship, Alexander Hollaender Distinguished Postdoctoral Fellowship (US)

OSTI Identifier:: 840978

Report Number(s):: LBNL-50371
R&D Project: LGFGAA; TRN: US200513%%195

DOE Contract Number:: AC03-76SF00098

Resource Type:: Journal Article

Journal Name:: Human Molecular Genetics

Additional Journal Information:: Journal Volume: 10; Journal Issue: 18; Other Information: Journal Publication Date: 2001; PBD: 5 Jul 2001

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; APOLIPOPROTEINS; APOPTOSIS; CATHEPSINS; DISEASES; GENES; HYBRIDIZATION; METALLOTHIONEIN; MICE; MUTATIONS; OLIGONUCLEOTIDES; PATHOLOGY; PATIENTS; POLYMERASE CHAIN REACTION; PROTEINS; PROTEOLYSIS

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                    Lieuallen, Kimberly, Pennacchio, Len A, Park, Morgan, Myers, Richard M, and Lennon, Gregory G. Cystatin B-deficient mice have increased expression of apoptosis and glial activation genes.  United States: N. p., 2001. 
        Web.  doi:10.1093/hmg/10.18.1867.

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                    Lieuallen, Kimberly, Pennacchio, Len A, Park, Morgan, Myers, Richard M, & Lennon, Gregory G. Cystatin B-deficient mice have increased expression of apoptosis and glial activation genes.  United States.  https://doi.org/10.1093/hmg/10.18.1867

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                    Lieuallen, Kimberly, Pennacchio, Len A, Park, Morgan, Myers, Richard M, and Lennon, Gregory G. 2001.  
        "Cystatin B-deficient mice have increased expression of apoptosis and glial activation genes".  United States.  https://doi.org/10.1093/hmg/10.18.1867.

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@article{osti_840978,

  title        = {Cystatin B-deficient mice have increased expression of apoptosis and glial activation genes},

  author       = {Lieuallen, Kimberly and Pennacchio, Len A and Park, Morgan and Myers, Richard M and Lennon, Gregory G},

  abstractNote = {Loss-of-function mutations in the cystatin B (Cstb) gene cause a neurological disorder known as Unverricht Lundborg disease (EPM1) in human patients. Mice that lack Cstb provide a mammalian model for EPM1 by displaying progressive ataxia and myoclonic seizures. We analyzed RNAs from brains of Cstb-deficient mice by using modified differential display, oligonucleotide microarray hybridization and quantitative reverse transcriptase polymerase chain reaction to examine the molecular consequences of the lack of Cstb. We identified seven genes that have consistently increased transcript levels in neurological tissues from the knockout mice. These genes are cathepsin S, C1q B-chain of complement (C1qB), beta-2-microglobulin, glial fibrillary acidic protein (Gfap), apolipoprotein D, fibronectin 1 and metallothionein II, which are expected to be involved in increased proteolysis, apoptosis and glial activation. The molecular changes in Cstb-deficient mice are consistent with the pathology found in the mouse model and may provide clues towards the identification of therapeutic points of intervention for EPM1 patients.},

  doi          = {10.1093/hmg/10.18.1867},

  url          = {https://www.osti.gov/biblio/840978},
  journal      = {Human Molecular Genetics},
number       = 18,

  volume       = 10,

  place        = {United States},

  year         = {Thu Jul 05 00:00:00 EDT 2001},

  month        = {Thu Jul 05 00:00:00 EDT 2001}

}

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