title: Cystatin B-deficient mice have increased expression of apoptosis and glial activation genes.
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), beta2-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.affiliation: Gene Logic Inc., 708 Quince Orchard Road, Gaithersburg, MD 20878, USA.
authors.forename: K
authors.initials: K
authors.lastname: Lieuallen
authors.forename: L A
authors.initials: LA
authors.lastname: Pennacchio
authors.forename: M
authors.initials: M
authors.lastname: Park
authors.forename: R M
authors.initials: RM
authors.lastname: Myers
authors.forename: G G
authors.initials: GG
authors.lastname: Lennon
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000235:genetics; D053399:Apolipoproteins D; D017209:Apoptosis / Q000235:genetics*; D015922:Complement C1q / Q000235:genetics; D055313:Cystatin B; D015891:Cystatins / Q000172:deficiency* / Q000235:genetics; D005353:Fibronectins / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009457:Neuroglia / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D001613:beta 2-Microglobulin / Q000235:genetics
chemical_list: D001053:Apolipoproteins; D053399:Apolipoproteins D; C524994:CSTB protein, human; C524992:Cstb protein, mouse; D015891:Cystatins; D005353:Fibronectins; D005904:Glial Fibrillary Acidic Protein; D001613:beta 2-Microglobulin; D012313:RNA; D015922:Complement C1q; D055313:Cystatin B; D008668:Metallothionein