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Frontiers in Biology

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Front. Biol.    2016, Vol. 11 Issue (3) : 151-167    https://doi.org/10.1007/s11515-016-1405-3
REVIEW
Transgenic mouse models for studying adult neurogenesis
Fatih Semerci1,2,Mirjana Maletic-Savatic1,2,3,*()
1. Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA
2. Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, TX 77030, USA
3. Department of Pediatrics-Neurology, Department of Neuroscience, and Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, TX 77030, USA
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Abstract

The mammalian hippocampus shows a remarkable capacity for continued neurogenesis throughout life. Newborn neurons, generated by the radial neural stem cells (NSCs), are important for learning and memory as well as mood control. During aging, the number and responses of NSCs to neurogenic stimuli diminish, leading to decreased neurogenesis and age-associated cognitive decline and psychiatric disorders. Thus, adult hippocampal neurogenesis has garnered significant interest because targeting it could be a novel potential therapeutic strategy for these disorders. However, if we are to use neurogenesis to halt or reverse hippocampal-related pathology, we need to understand better the core molecular machinery that governs NSC and their progeny. In this review, we summarize a wide variety of mouse models used in adult neurogenesis field, present their advantages and disadvantages based on specificity and efficiency of labeling of different cell types, and review their contribution to our understanding of the biology and the heterogeneity of different cell types found in adult neurogenic niches.
Keywords adult neurogenesis      mouse models      neural stem cells      neuroprogenitors      lineage tracing     
Corresponding Author(s): Mirjana Maletic-Savatic   
Just Accepted Date: 25 May 2016   Online First Date: 23 June 2016    Issue Date: 05 July 2016
 Cite this article:   
Fatih Semerci,Mirjana Maletic-Savatic. Transgenic mouse models for studying adult neurogenesis[J]. Front. Biol., 2016, 11(3): 151-167.
 URL:  
https://academic.hep.com.cn/fib/EN/10.1007/s11515-016-1405-3
https://academic.hep.com.cn/fib/EN/Y2016/V11/I3/151
Fig.1  Summary of immunohistochemical markers, reporter and lineage tracing mouse models used to identify different cell types of the adult hippocampal neurogenic niche. NSC, neural stem cells; RGL, radial glia like cells; ANP, amplifying neuroprogenitors; IPC, intermediate progenitor cells. Upper part: Markers, Middle part: Reporter lines; Lower part: Lineage tracing lines. * denotes the mouse models that target mostly quiescent neural stem cells.
Fig.2  Summary of immunohistochemical markers, reporter and lineage tracing mouse models used to identify different cell types of the adult subventricular zone neurogenic niche. Broken strip (EGFR) indicates expression in only subset of Type B cells. EGFR+ population is actively cycling whereas EGFR− population consists of quiescent SVZ neural stem cells. SVZ= subventricular zone; RMS= rostral migratory stream; OB= olfactory bulb. Upper part: Markers, Middle part: Reporter lines; Lower part: Lineage tracing lines.
Line Use Reference
Nestin Nestin::lacZ Characterization of regulatory regions of Nestin Zimmerman et al., 1994; Johansson et al., 2002
Nestin::CFPnuc Quantification of NSCs and progenitor cells Encinas et al., 2006
Nestin::GFP, Nestin::eGFP Population studies of NSCs and progenitor cells Yamaguchi et al., 2000; Kawaguchi et al., 2001; Mignone et al., 2004
Nestin::tTA, Nestin-rtTA, Nestin-rtTA-M2-eGFPNestin-Cre, Nestin-CreER; Nestin-CreERT2 Lineage tracing Mitsuhashi et al., 2001; Beech et al., 2004; Yu et al., 2005Betz et al., 1996; Kuo et al., 2006; Imayoshi et al., 2006; Lagace et al., 2007; Dranovsky et al., 2011
GFAP GFAP::GFP, GFAP::eGFP GFAP::AmCyan1, AsRed2, mRFP1 Population studies of astrocytes and NSCs Zhuo et al., 1997; Nolte et al., 2001; Hirrlinger et al., 2005; Platel et al., 2009
GFAP::TK Specific ablation of NSCs Garcia et al., 2004
GFAP-Cre, GFAP-CreERT2 Lineage tracing of NSCs Marino et al., 2000; Casper and McCarthy, 2006; Ganat et al., 2006
Sox1 Sox1-GFP Population studies of a subset of NSCs and ANPs Aubert et al., 2003
Sox1-tTA;tetO-Cre Lineage tracing of NSCs and ANPs Venere et al., 2012
Sox2 Sox2β-Geo Strong activity in SVZ but weak in SGZ Zappone et al., 2000
Sox2::GFP, Sox2-eGFP Population studies of NSCs, ANPs, and astrocytes D'Amour and Gage, 2003; Ellis et al., 2004
Sox2::Cre, Sox2::CreER, Sox2::CreERT2 Lineage tracing Hayashi et al., 2007; Favaro et al., 2009; Kang and Hebert, 2012
Ascl1 Ascl1-GFPnuc Strong expression in ANPs but weak in NSCs Leung et al., 2007
Ascl1-CreERT2 Lineage tracing in SGZ Kim et al., 2011
Glast Glast::eGFP Glast::dsRed Population studies of astrocytes and NSCs Gong et al., 2003 Glowatzki et al., 2006; Regan et al., 2007
Glast-CreERT2; Glast::CreERT2 Lineage tracing Mori et al., 2006; Slezak et al., 2007
Blbp Blbp::GFP, BLBP::eGFPBlbp::eYFP, Blbp::dsRed2Blbp::mCherry Population studies of astrocytes and NSCs Gong et al., 2003;Anthony et al., 2004; Schmid et al., 2006; Giachino et al., 2014
Blbp::Cre Lineage tracing Anthony et al., 2004; Hegedus et al., 2007
Hes5 Hes5::GFP Population studies of a subset of NSCs and ANPs Basak and Taylor, 2007
Hes5::CreERT2 Lineage tracing Lugert et al., 2012
Tbr2 EOMES::GFP Labeling of late ANPs and early NBs Kwon and Hadjantonakis, 2007
Tbr2::GFP Labeling of late ANPs, NBs, INs and some GCs Gong et al., 2003
EOMES-CreERT2Tbr2::CreERT2 Lineage tracing of late ANPs and NBs Pimeisl et al., 2013 Berg et al., 2015
Spot14 Spot14::GFP Labeling of subset of NSCs and ANPs Knobloch et al., 2013; Knobloch et al., 2014
Spot14::CreERT2 Lineage tracing Knobloch et al., 2013
Gli1 Gli1::CreERT2 Lineage tracing of NSCs in SGZ Ahn and Joyner, 2004
Prss56 Prss56-CreERT2 Lineage tracing of NSCs in SGZ Jourdon et al., 2015
Hopx Hopx-3FlagGFP/+ Labeling of NSCs of SGZ Li et al., 2015
Hopx-ERCre/+ Lineage tracing of NSCs in SGZ Li et al., 2015
Tctex-1 Tctex-1::GFP, Tctex-1::DsRed Labeling of NSCs, ANPs and NBs of SGZ Tseng et al., 2010
Pomc Pomc::eGFP Labeling of NBs/INs Cowley et al., 2001
Pomc-Cre Lineage tracing of NBs/INs Balthasar et al., 2004
Dcx Dcx-eGFP Dcx-DsRed Labeling of NBs/INs Labeling of NBs/INs Couillard-Despres et al., 2006; Walker et al., 2007 Couillard-Despres et al., 2006; Wang et al., 2007
Tab.1  List of reporter mice used in adult neurogenesis research.
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