Decrease in excitatory neurons, astrocytes and proliferating progenitors in the cerebral cortex of mice lacking exon 3 from the Fgf2 gene

Persistent Link:
http://hdl.handle.net/10150/610071
Title:
Decrease in excitatory neurons, astrocytes and proliferating progenitors in the cerebral cortex of mice lacking exon 3 from the Fgf2 gene
Author:
Chen, Kesi; Ohkubo, Yasushi; Shin, Dana; Doetschman, Thomas; Sanford, L. P.; Li, Hongqi; Vaccarino, Flora
Affiliation:
Child Study Center, Yale University School of Medicine, 230 South Frontage Rd, New Haven CT 06520, USA; University of Arizona, 1656 E Mabel St, PO Box 245217, Tucson, AZ 85724-5217, USA; Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
Issue Date:
2008
Publisher:
BioMed Central
Citation:
BMC Neuroscience 2008, 9:94 doi:10.1186/1471-2202-9-94
Journal:
BMC Neuroscience
Rights:
© 2008 Chen et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
BACKGROUND:The Fgf2 gene is expressed in the brain neuroepithelium during embryonic development and in astroglial cells throughout life. Previous knockout studies suggested that FGF2 plays a role in the proliferation of neural progenitors in the embryonic cerebral cortex. These studies exclusively used knockout alleles lacking the Fgf2 exon 1. However, the description of putative alternative exons located downstream from the canonical exon 1 raised the possibility that alternatively spliced transcripts may compensate for the lack of the canonical exon 1 in the Fgf2 -/- mice.RESULTS:We generated and characterized a new line of Fgf2 knockout mice lacking the expression of exon 3, which is conserved in all Fgf2 transcripts and contains essential heparin and receptor binding interfaces. The expression of Fgf2 exon 3 was prevented by inserting a transcriptional STOP cassette in the Fgf2 genomic locus. These mice demonstrate a phenotype in the adult neocortex characterized by decreased density and number of cortical excitatory neurons and astrocytes, which is virtually identical to that of the Fgf2 -/- mice lacking exon 1. In addition, we also show that the Fgf2 exon 3 knockout mice have decreased proliferation of precursors in the adult cerebral cortex, which had not been previously investigated in the other mutant lines.CONCLUSION:The results demonstrate that the phenotype of two completely different Fgf2 KO mouse lines, lacking exon 1 or exon 3, is remarkably similar. The combined results from these KO models clearly indicate that FGF2 plays a role in cortical cell genesis during embryonic development as well as in adulthood. Thus, FGF2 may be required for the maintenance of the pool of adult cortical progenitor cells.
EISSN:
1471-2202
DOI:
10.1186/1471-2202-9-94
Version:
Final published version
Additional Links:
http://www.biomedcentral.com/1471-2202/9/94

Full metadata record

DC FieldValue Language
dc.contributor.authorChen, Kesien
dc.contributor.authorOhkubo, Yasushien
dc.contributor.authorShin, Danaen
dc.contributor.authorDoetschman, Thomasen
dc.contributor.authorSanford, L. P.en
dc.contributor.authorLi, Hongqien
dc.contributor.authorVaccarino, Floraen
dc.date.accessioned2016-05-20T08:57:54Z-
dc.date.available2016-05-20T08:57:54Z-
dc.date.issued2008en
dc.identifier.citationBMC Neuroscience 2008, 9:94 doi:10.1186/1471-2202-9-94en
dc.identifier.doi10.1186/1471-2202-9-94en
dc.identifier.urihttp://hdl.handle.net/10150/610071-
dc.description.abstractBACKGROUND:The Fgf2 gene is expressed in the brain neuroepithelium during embryonic development and in astroglial cells throughout life. Previous knockout studies suggested that FGF2 plays a role in the proliferation of neural progenitors in the embryonic cerebral cortex. These studies exclusively used knockout alleles lacking the Fgf2 exon 1. However, the description of putative alternative exons located downstream from the canonical exon 1 raised the possibility that alternatively spliced transcripts may compensate for the lack of the canonical exon 1 in the Fgf2 -/- mice.RESULTS:We generated and characterized a new line of Fgf2 knockout mice lacking the expression of exon 3, which is conserved in all Fgf2 transcripts and contains essential heparin and receptor binding interfaces. The expression of Fgf2 exon 3 was prevented by inserting a transcriptional STOP cassette in the Fgf2 genomic locus. These mice demonstrate a phenotype in the adult neocortex characterized by decreased density and number of cortical excitatory neurons and astrocytes, which is virtually identical to that of the Fgf2 -/- mice lacking exon 1. In addition, we also show that the Fgf2 exon 3 knockout mice have decreased proliferation of precursors in the adult cerebral cortex, which had not been previously investigated in the other mutant lines.CONCLUSION:The results demonstrate that the phenotype of two completely different Fgf2 KO mouse lines, lacking exon 1 or exon 3, is remarkably similar. The combined results from these KO models clearly indicate that FGF2 plays a role in cortical cell genesis during embryonic development as well as in adulthood. Thus, FGF2 may be required for the maintenance of the pool of adult cortical progenitor cells.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.biomedcentral.com/1471-2202/9/94en
dc.rights© 2008 Chen et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.titleDecrease in excitatory neurons, astrocytes and proliferating progenitors in the cerebral cortex of mice lacking exon 3 from the Fgf2 geneen
dc.typeArticleen
dc.identifier.eissn1471-2202en
dc.contributor.departmentChild Study Center, Yale University School of Medicine, 230 South Frontage Rd, New Haven CT 06520, USAen
dc.contributor.departmentUniversity of Arizona, 1656 E Mabel St, PO Box 245217, Tucson, AZ 85724-5217, USAen
dc.contributor.departmentDepartment of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USAen
dc.identifier.journalBMC Neuroscienceen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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