CD11c/EYFP transgene illuminates a discrete network of dendritic cells within the embryonic, neonatal, adult, and injured mouse brain

The CD11c enhanced yellow fluorescent protein (EYFP) transgenic mouse was constructed to identify dendritic cells in the periphery (Lindquist et al. [2004] Nat. Immunol. 5:1243–1250). In this study, we used this mouse to characterize dendritic cells within the CNS. Our anatomic results showed discre...

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Veröffentlicht in:Journal of comparative neurology (1911) 2008-06, Vol.508 (5), p.687-710
Hauptverfasser: Bulloch, Karen, Miller, Melinda M., Gal-Toth, Judit, Milner, Teresa A., Gottfried-Blackmore, Andres, Waters, Elizabeth M., Kaunzner, Ulrike W., Liu, Kang, Lindquist, Randall, Nussenzweig, Michel C., Steinman, Ralph M., McEwen, Bruce S.
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container_end_page 710
container_issue 5
container_start_page 687
container_title Journal of comparative neurology (1911)
container_volume 508
creator Bulloch, Karen
Miller, Melinda M.
Gal-Toth, Judit
Milner, Teresa A.
Gottfried-Blackmore, Andres
Waters, Elizabeth M.
Kaunzner, Ulrike W.
Liu, Kang
Lindquist, Randall
Nussenzweig, Michel C.
Steinman, Ralph M.
McEwen, Bruce S.
description The CD11c enhanced yellow fluorescent protein (EYFP) transgenic mouse was constructed to identify dendritic cells in the periphery (Lindquist et al. [2004] Nat. Immunol. 5:1243–1250). In this study, we used this mouse to characterize dendritic cells within the CNS. Our anatomic results showed discrete populations of EYFP+ brain dendritic cells (EYFP+ bDC) that colocalized with a small fraction of microglia immunoreactive for Mac‐1, Iba‐1, CD45, and F4/80 but not for NeuN, Dcx, NG2 proteoglycan, or GFAP. EYFP+ bDC, isolated by fluorescent activated cell sorting (FACS), expressed mRNA for the Itgax (CD11c) gene, whereas FACS anlaysis of EYFP+ bDC cultures revealed the presence of CD11c protein. Light microscopy studies revealed that EYFP+ bDC were present in the embryonic CNS when the blood–brain barrier is formed and postnatally when brain cells are amenable to culturing. In adult male mice, EYFP+ bDC distribution was prominent within regions of the CNS that 1) are subject to structural plasticity and neurogenesis, 2) receive sensory and humoral input from the external environment, and 3) lack a blood–brain barrier. Ultrastructural analysis of EYFP+ bDC in adult neurogenic niches showed their proximity to developing neurons and a morphology characteristic of immune/microglia cells. Kainic acid‐induced seizures revealed that EYFP+ bDC responded to damage of the hippocampus and displayed morphologies similar to those described for seizure‐activated EGFP+ microglia in the hippocampus of cfms (CSF‐1R) EGFP mice. Collectively, these findings suggest a new member of the dendritic cell family residing among the heterogeneous microglia population. J. Comp. Neurol. 508:687–710, 2008. © 2008 Wiley‐Liss, Inc.
doi_str_mv 10.1002/cne.21668
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[2004] Nat. Immunol. 5:1243–1250). In this study, we used this mouse to characterize dendritic cells within the CNS. Our anatomic results showed discrete populations of EYFP+ brain dendritic cells (EYFP+ bDC) that colocalized with a small fraction of microglia immunoreactive for Mac‐1, Iba‐1, CD45, and F4/80 but not for NeuN, Dcx, NG2 proteoglycan, or GFAP. EYFP+ bDC, isolated by fluorescent activated cell sorting (FACS), expressed mRNA for the Itgax (CD11c) gene, whereas FACS anlaysis of EYFP+ bDC cultures revealed the presence of CD11c protein. Light microscopy studies revealed that EYFP+ bDC were present in the embryonic CNS when the blood–brain barrier is formed and postnatally when brain cells are amenable to culturing. In adult male mice, EYFP+ bDC distribution was prominent within regions of the CNS that 1) are subject to structural plasticity and neurogenesis, 2) receive sensory and humoral input from the external environment, and 3) lack a blood–brain barrier. Ultrastructural analysis of EYFP+ bDC in adult neurogenic niches showed their proximity to developing neurons and a morphology characteristic of immune/microglia cells. Kainic acid‐induced seizures revealed that EYFP+ bDC responded to damage of the hippocampus and displayed morphologies similar to those described for seizure‐activated EGFP+ microglia in the hippocampus of cfms (CSF‐1R) EGFP mice. Collectively, these findings suggest a new member of the dendritic cell family residing among the heterogeneous microglia population. J. Comp. Neurol. 508:687–710, 2008. © 2008 Wiley‐Liss, Inc.</description><identifier>ISSN: 0021-9967</identifier><identifier>EISSN: 1096-9861</identifier><identifier>DOI: 10.1002/cne.21668</identifier><identifier>PMID: 18386786</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Age Factors ; Animals ; Animals, Newborn ; Bacterial Proteins - analysis ; Bacterial Proteins - biosynthesis ; Bacterial Proteins - genetics ; Brain - cytology ; Brain - embryology ; Brain - physiology ; Brain Injuries - genetics ; Brain Injuries - metabolism ; Brain Injuries - pathology ; CD11c Antigen - analysis ; CD11c Antigen - biosynthesis ; CD11c Antigen - genetics ; Cells, Cultured ; central nervous system ; Dendritic Cells - cytology ; Dendritic Cells - physiology ; Female ; immune system ; Luminescent Proteins - analysis ; Luminescent Proteins - biosynthesis ; Luminescent Proteins - genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Mice, Transgenic ; neurogenesis ; Pregnancy ; steady state ; Transgenes - physiology ; transgenic mouse</subject><ispartof>Journal of comparative neurology (1911), 2008-06, Vol.508 (5), p.687-710</ispartof><rights>Copyright © 2008 Wiley‐Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4278-d51aef3d1558c0cc2d0d49bd37514bb51e4094a3eb443ca1c52f90e84245ebc43</citedby><cites>FETCH-LOGICAL-c4278-d51aef3d1558c0cc2d0d49bd37514bb51e4094a3eb443ca1c52f90e84245ebc43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcne.21668$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcne.21668$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18386786$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bulloch, Karen</creatorcontrib><creatorcontrib>Miller, Melinda M.</creatorcontrib><creatorcontrib>Gal-Toth, Judit</creatorcontrib><creatorcontrib>Milner, Teresa A.</creatorcontrib><creatorcontrib>Gottfried-Blackmore, Andres</creatorcontrib><creatorcontrib>Waters, Elizabeth M.</creatorcontrib><creatorcontrib>Kaunzner, Ulrike W.</creatorcontrib><creatorcontrib>Liu, Kang</creatorcontrib><creatorcontrib>Lindquist, Randall</creatorcontrib><creatorcontrib>Nussenzweig, Michel C.</creatorcontrib><creatorcontrib>Steinman, Ralph M.</creatorcontrib><creatorcontrib>McEwen, Bruce S.</creatorcontrib><title>CD11c/EYFP transgene illuminates a discrete network of dendritic cells within the embryonic, neonatal, adult, and injured mouse brain</title><title>Journal of comparative neurology (1911)</title><addtitle>J. Comp. Neurol</addtitle><description>The CD11c enhanced yellow fluorescent protein (EYFP) transgenic mouse was constructed to identify dendritic cells in the periphery (Lindquist et al. [2004] Nat. Immunol. 5:1243–1250). In this study, we used this mouse to characterize dendritic cells within the CNS. Our anatomic results showed discrete populations of EYFP+ brain dendritic cells (EYFP+ bDC) that colocalized with a small fraction of microglia immunoreactive for Mac‐1, Iba‐1, CD45, and F4/80 but not for NeuN, Dcx, NG2 proteoglycan, or GFAP. EYFP+ bDC, isolated by fluorescent activated cell sorting (FACS), expressed mRNA for the Itgax (CD11c) gene, whereas FACS anlaysis of EYFP+ bDC cultures revealed the presence of CD11c protein. Light microscopy studies revealed that EYFP+ bDC were present in the embryonic CNS when the blood–brain barrier is formed and postnatally when brain cells are amenable to culturing. 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Comp. Neurol</addtitle><date>2008-06-10</date><risdate>2008</risdate><volume>508</volume><issue>5</issue><spage>687</spage><epage>710</epage><pages>687-710</pages><issn>0021-9967</issn><eissn>1096-9861</eissn><abstract>The CD11c enhanced yellow fluorescent protein (EYFP) transgenic mouse was constructed to identify dendritic cells in the periphery (Lindquist et al. [2004] Nat. Immunol. 5:1243–1250). In this study, we used this mouse to characterize dendritic cells within the CNS. Our anatomic results showed discrete populations of EYFP+ brain dendritic cells (EYFP+ bDC) that colocalized with a small fraction of microglia immunoreactive for Mac‐1, Iba‐1, CD45, and F4/80 but not for NeuN, Dcx, NG2 proteoglycan, or GFAP. EYFP+ bDC, isolated by fluorescent activated cell sorting (FACS), expressed mRNA for the Itgax (CD11c) gene, whereas FACS anlaysis of EYFP+ bDC cultures revealed the presence of CD11c protein. Light microscopy studies revealed that EYFP+ bDC were present in the embryonic CNS when the blood–brain barrier is formed and postnatally when brain cells are amenable to culturing. In adult male mice, EYFP+ bDC distribution was prominent within regions of the CNS that 1) are subject to structural plasticity and neurogenesis, 2) receive sensory and humoral input from the external environment, and 3) lack a blood–brain barrier. Ultrastructural analysis of EYFP+ bDC in adult neurogenic niches showed their proximity to developing neurons and a morphology characteristic of immune/microglia cells. Kainic acid‐induced seizures revealed that EYFP+ bDC responded to damage of the hippocampus and displayed morphologies similar to those described for seizure‐activated EGFP+ microglia in the hippocampus of cfms (CSF‐1R) EGFP mice. Collectively, these findings suggest a new member of the dendritic cell family residing among the heterogeneous microglia population. J. Comp. Neurol. 508:687–710, 2008. © 2008 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>18386786</pmid><doi>10.1002/cne.21668</doi><tpages>24</tpages></addata></record>
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ispartof Journal of comparative neurology (1911), 2008-06, Vol.508 (5), p.687-710
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subjects Age Factors
Animals
Animals, Newborn
Bacterial Proteins - analysis
Bacterial Proteins - biosynthesis
Bacterial Proteins - genetics
Brain - cytology
Brain - embryology
Brain - physiology
Brain Injuries - genetics
Brain Injuries - metabolism
Brain Injuries - pathology
CD11c Antigen - analysis
CD11c Antigen - biosynthesis
CD11c Antigen - genetics
Cells, Cultured
central nervous system
Dendritic Cells - cytology
Dendritic Cells - physiology
Female
immune system
Luminescent Proteins - analysis
Luminescent Proteins - biosynthesis
Luminescent Proteins - genetics
Male
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Transgenic
neurogenesis
Pregnancy
steady state
Transgenes - physiology
transgenic mouse
title CD11c/EYFP transgene illuminates a discrete network of dendritic cells within the embryonic, neonatal, adult, and injured mouse brain
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