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Loss of arginase I results in increased proliferation of neural stem cells
Author(s) -
BeckerCatania Sara G.,
Gregory Teresa L.,
Yang Yawei,
Gau ChiaLing,
de Vellis Jean,
Cederbaum Stephen D.,
Iyer Ramaswamy K.
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20964
Subject(s) - arginase , neural stem cell , biology , glial fibrillary acidic protein , microbiology and biotechnology , stem cell , wild type , astrocyte , cell type , neurosphere , cellular differentiation , cell growth , arginine , endocrinology , cell , immunology , biochemistry , adult stem cell , amino acid , central nervous system , immunohistochemistry , gene , mutant
Loss of arginase I (AI) results in a metabolic disorder characterized by growth retardation, increased mental impairment and spasticity, and potentially fatal hyperammonemia. This syndrome plus a growing body of evidence supports a role for arginase and arginine metabolites in normal neuronal development and function. Here we report our initial observations of the effects of AI loss on proliferation and differentiation of neural stem cells (NSCs) isolated from the germinal zones of embryonic and newborn AI knockout (KO) mice compared with heterozygous (HET) and wild‐type (WT) control animals. By using both short and long‐term proliferation assays (3 and 10 days, respectively), we found a 1.5–2‐fold increase in the number of KO cells compared with WT. FACS analysis showed an increase in KO cells in the synthesis phase of the cell cycle vs. WT cells. After NSC differentiation, AI‐deficient cells expressed β‐tubulin, SMI81 (SNAP25), glial fibrillary acidic protein, and CNPase, which are markers consistent with neurons, astrocytes, and oligodendrocytes. Many KO cells exhibited a more mature morphology and expressed mature neuronal markers that were decreased or not present in HET or WT cells. Limited, comparative expression array and quantitative RT‐PCR analysis identified differences in the levels of several mRNAs encoding structural, signaling, and arginine metabolism proteins between KO and WT cells. The consequence of these changes may contribute to the differential phenotypes of KO vs. WT cells. It appears that AI may play an important and unanticipated role in growth and development of NSCs. © 2006 Wiley‐Liss, Inc.