cDNA cloning, chromosomal localization, and expression analysis of human BEHAB/brevican, a brain specific proteoglycan regulated during cortical development and in glioma.
Open accessAbstract
BEHAB (Brain Enriched HyAluronan Binding)/brevican, a brain-specific member of the lectican family of chondroitin sulfate proteoglycans (CSPGs), may play a role in both brain development and human glioma. BEHAB/brevican has been cloned from bovine, mouse and rat. Two isoforms have been reported: a full-length isoform that is secreted into the extracellular matrix (ECM) and a shorter isoform with a sequence that predicts a glycophosphatidylinositol (GPI) anchor. Here, we report the characterization of BEHAB/brevican isoforms in human brain. First, BEHAB/brevican maps to human chromosome 1q31. Second, we report the sequence of both isoforms of human BEHAB/brevican. The deduced protein sequence of full-length, secreted human BEHAB/brevican is 89.7, 83.3 and 83.2% identical to bovine, mouse and rat homologues, respectively. Third, by RNase protection analysis (RPA) we show the developmental regulation of BEHAB/brevican isoforms in normal human cortex. The secreted isoform is highly expressed from birth through 8years of age and is downregulated by 20years of age to low levels that are maintained in the normal adult cortex. The GPI isoform is expressed at uniformly low levels throughout development. Fourth, we confirm and extend previous studies from our laboratory, here demonstrating the upregulation of BEHAB/brevican mRNA in human glioma quantitatively. RPA analysis shows that both isoforms are upregulated in glioma, showing an approximately sevenfold increase in expression over normal levels. In contrast to the developmental regulation of BEHAB/brevican, where only the secreted isoform is regulated, both isoforms are increased in parallel in human glioma. The distinct patterns of regulation of expression of the two isoforms suggest distinct mechanisms of regulation of BEHAB/brevican during development and in glioma.
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High levels of brevican mRNA expression were detected in postmortem human cortex during early development until 8 years of age, and expression levels were lower in the adult human brain.
“For example, high levels of brevican mRNA expression were detected in postmortem human cortex during early development until 8 years of age, and the expression levels were lower in the adult human brain (Gary et al., 2000).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Gary et al., 2000
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- Authors
- Gary, S. C., Zerillo, C. A., Chiang, V. L., Gaw, J. U., Gray, G., & Hockfield, S.
- Affiliations
- Yale University (US)
- Corresponding author
- Gary, Sydney C.
- ORCID
- Chiang, Veronica L.
- Venue
- Gene
- Publisher
- Elsevier BV
- Published
- 2000-10
- Volume
- 256
- Issue
- 1-2
- Pages
- 139-147
- ISSN
- 0378-1119 (ISSN-L)
- OpenAlex
- W2083857472
- Cited by
- 36
- References
- 28
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2014: 2 · 2013: 1 · 2012: 3
- FWCI
- 0.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- Locations
- Gene (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Eye Institute (EY 06511)
- National Institute of Neurological Disorders and Stroke (NS35228, R01NS035228)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Keywords
- brevican, chondroitin sulfate proteoglycans, lecticans, cDNA cloning, gene mapping, cortical development, brain development, glioma, gene expression regulation, extracellular matrix, human brain
- MeSH terms
- Amino Acid Sequence, Base Sequence, Brain, Carrier Proteins, Cerebral Cortex, Chromosome Mapping, Chromosomes, Human, Pair 1, Cloning, Molecular, Glioma, Humans, Molecular Sequence Data, Nerve Tissue Proteins, Chondroitin Sulfate Proteoglycans, Proteoglycans, RNA, Transcription, Genetic, Gene Expression, Gene Expression Regulation, Neoplastic, DNA, Complementary, Gene Expression Regulation, Developmental, Protein Isoforms, Lectins, C-Type, Brevican
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