Skip to main content
SpringerLink
Log in
Book cover

Multidisciplinary Tools for Investigating Synaptic Plasticity pp 3–41Cite as

Conditional Gene Targeting: A Refined Method for Genetic Studies in Neurosciences

  • Protocol
  • First Online:

  • 920 Accesses

Part of the book series: Neuromethods ((NM,volume 81))

Abstract

Conditional mutagenesis in mice is a key approach in neurosciences that makes it possible to investigate the functions of defined genes within certain neural subpopulations. The approach is based on the combination of transgenic expression of a recombinase with targeted candidate genes containing recognition sequences of this recombinase generated by gene targeting. Here we describe three major recombination systems, the Cre/loxP, Flp/FRT, and Dre/rox, and present a procedure that allows the generation of target alleles for these systems. We provide detailed protocols for the culture and transfection of embryonic stem (ES) cells and for the identification and confirmation of homologous recombinants. This chapter also provides an overview of recent developments such as gene targeting in oocytes and discusses future perspectives.

This is a preview of subscription content, log in via an institution.

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Waterston RH et al (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420:520–562

    Article  PubMed  CAS  Google Scholar 

  2. Li Y, Erzurumlu RS, Chen C, Jhaveri S, Tonegawa S (1994) Whisker-related neuronal patterns fail to develop in the trigeminal brainstem nuclei of NMDAR1 knockout mice. Cell 76:427–437

    Article  PubMed  CAS  Google Scholar 

  3. Forrest D et al (1994) Targeted disruption of NMDA receptor 1 gene abolishes NMDA response and results in neonatal death. Neuron 13:325–338

    Article  PubMed  CAS  Google Scholar 

  4. Gondo Y, Fukumura R, Murata T, Makino S (2009) Next-generation gene targeting in the mouse for functional genomics. BMB Rep 42:315–323

    Article  PubMed  CAS  Google Scholar 

  5. Schwenk F, Kuhn R, Angrand PO, Rajewsky K, Stewart AF (1998) Temporally and spatially regulated somatic mutagenesis in mice. Nucleic Acids Res 26:1427–1432

    Article  PubMed  CAS  Google Scholar 

  6. Metzger D, Clifford J, Chiba H, Chambon P (1995) Conditional site-specific recombination in mammalian cells using a ligand-dependent chimeric Cre recombinase. Proc Natl Acad Sci USA 92:6991–6995

    Article  PubMed  CAS  Google Scholar 

  7. Capecchi MR (2005) Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century. Nat Rev Genet 6:507–512

    Article  PubMed  CAS  Google Scholar 

  8. Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156

    Article  PubMed  CAS  Google Scholar 

  9. Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 78:7634–7638

    Article  PubMed  CAS  Google Scholar 

  10. Bradley A, Evans M, Kaufman MH, Robertson E (1984) Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines. Nature 309:255–256

    Article  PubMed  CAS  Google Scholar 

  11. Robertson E, Bradley A, Kuehn M, Evans M (1986) Germ-line transmission of genes introduced into cultured pluripotential cells by retroviral vector. Nature 323:445–448

    Article  PubMed  CAS  Google Scholar 

  12. Gossler A, Doetschman T, Korn R, Serfling E, Kemler R (1986) Transgenesis by means of blastocyst-derived embryonic stem cell lines. Proc Natl Acad Sci USA 83:9065–9069

    Article  PubMed  CAS  Google Scholar 

  13. Zijlstra M, Li E, Sajjadi F, Subramani S, Jaenisch R (1989) Germ-line transmission of a disrupted beta 2-microglobulin gene produced by homologous recombination in embryonic stem cells. Nature 342:435–438

    Article  PubMed  CAS  Google Scholar 

  14. Schwartzberg PL, Goff SP, Robertson EJ (1989) Germ-line transmission of a c-abl mutation produced by targeted gene disruption in ES cells. Science 246:799–803

    Article  PubMed  CAS  Google Scholar 

  15. Thomas KR, Capecchi MR (1987) Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51: 503–512

    Article  PubMed  CAS  Google Scholar 

  16. Haenisch B, Bonisch H (2011) Depression and antidepressants: insights from knockout of dopamine, serotonin or noradrenaline re-uptake transporters. Pharmacol Ther 129: 352–368

    Article  PubMed  CAS  Google Scholar 

  17. King MV, Marsden CA, Fone KC (2008) A role for the 5-HT(1A), 5-HT(4) and 5-HT(6) receptors in learning and memory. Trends Pharmacol Sci 29(9):482–492

    Article  PubMed  CAS  Google Scholar 

  18. Crawley JN (2008) Behavioral phenotyping strategies for mutant mice. Neuron 57:809–818

    Article  PubMed  CAS  Google Scholar 

  19. Sternberg N, Hamilton D (1981) Bacteriophage P1 site-specific recombination. I. Recombination between loxP sites. J Mol Biol 150:467–486

    Article  PubMed  CAS  Google Scholar 

  20. Hoess RH, Ziese M, Sternberg N (1982) P1 site-specific recombination: nucleotide sequence of the recombining sites. Proc Natl Acad Sci USA 79:3398–3402

    Article  PubMed  CAS  Google Scholar 

  21. Argos P et al (1986) The integrase family of site-specific recombinases: regional similarities and global diversity. EMBO J 5:433–440

    PubMed  CAS  Google Scholar 

  22. Guo F, Gopaul DN, van Duyne GD (1997) Structure of Cre recombinase complexed with DNA in a site-specific recombination synapse. Nature 389:40–46

    Article  PubMed  CAS  Google Scholar 

  23. Feil R et al (1996) Ligand-activated site-specific recombination in mice. Proc Natl Acad Sci USA 93:10887–10890

    Article  PubMed  CAS  Google Scholar 

  24. Kilby NJ, Snaith MR, Murray JA (1993) Site-specific recombinases: tools for genome engineering. Trends Genet 9:413–421

    Article  PubMed  CAS  Google Scholar 

  25. Zhu XD, Pan G, Luetke K, Sadowski PD (1995) Homology requirements for ligation and strand exchange by the FLP recombinase. J Biol Chem 270:11646–11653

    Article  PubMed  CAS  Google Scholar 

  26. Buchholz F, Ringrose L, Angrand PO, Rossi F, Stewart AF (1996) Different thermostabilities of FLP and Cre recombinases: implications for applied site specific recombination. Nucleic Acids Res 24:4256–4262

    Article  PubMed  CAS  Google Scholar 

  27. Schaft J, Ashery-Padan R, van der Hoeven F, Gruss P, Stewart AF (2001) Efficient FLP recombination in mouse ES cells and oocytes. Genesis 31:6–10

    Article  PubMed  CAS  Google Scholar 

  28. Wu Y, Wang C, Sun H, LeRoith D, Yakar S (2009) High-efficient FLPo deleter mice in C57BL/6J background. PLoS One 4:e8054

    Article  PubMed  CAS  Google Scholar 

  29. Raymond CS, Soriano P (2007) High-efficiency FLP and PhiC31 site-specific recombination in mammalian cells. PLoS One 2:e162

    Article  PubMed  CAS  Google Scholar 

  30. Sauer B, McDermott J (2004) DNA recombination with a heterospecific Cre homolog identified from comparison of the pac-c1 regions of P1-related phages. Nucleic Acids Res 32:6086–6095

    Article  PubMed  CAS  Google Scholar 

  31. Anastassiadis K et al (2009) Dre recombinase, like Cre, is a highly efficient site-specific recombinase in E. coli, mammalian cells and mice. Dis Model Mech 2:508–515

    Article  PubMed  CAS  Google Scholar 

  32. Moon AM, Capecchi MR (2000) Fgf8 is required for outgrowth and patterning of the limbs. Nat Genet 26:455–459

    Article  PubMed  CAS  Google Scholar 

  33. Rodriguez CI, Dymecki SM (2000) Origin of the precerebellar system. Neuron 27: 475–486

    Article  PubMed  CAS  Google Scholar 

  34. Awatramani R, Soriano P, Rodriguez C, Mai JJ, Dymecki SM (2003) Cryptic boundaries in roof plate and choroid plexus identified by intersectional gene activation. Nat Genet 35:70–75

    Article  PubMed  CAS  Google Scholar 

  35. Capecchi MR (1989) Altering the genome by homologous recombination. Science 244: 1288–1292

    Article  PubMed  CAS  Google Scholar 

  36. Adams DJ et al (2004) Mutagenic insertion and chromosome engineering resource (MICER). Nat Genet 36:867–871

    Article  PubMed  CAS  Google Scholar 

  37. Soriano P (1999) Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet 21:70–71

    Article  PubMed  CAS  Google Scholar 

  38. Buch T et al (2005) A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration. Nat Methods 2:419–426

    Article  PubMed  CAS  Google Scholar 

  39. Valenzuela DM et al (2003) High-throughput engineering of the mouse genome coupled with high-resolution expression analysis. Nat Biotechnol 21:652–659

    Article  PubMed  CAS  Google Scholar 

  40. Gomez-Rodriguez J et al (2008) Advantages of q-PCR as a method of screening for gene targeting in mammalian cells using conventional and whole BAC-based constructs. Nucleic Acids Res 36:e117

    Article  PubMed  CAS  Google Scholar 

  41. Pettitt SJ et al (2009) Agouti C57BL/6N embryonic stem cells for mouse genetic resources. Nat Methods 6:493–495

    Article  PubMed  CAS  Google Scholar 

  42. Kontgen F, Suss G, Stewart C, Steinmetz M, Bluethmann H (1993) Targeted disruption of the MHC class II Aa gene in C57BL/6 mice. Int Immunol 5:957–964

    Article  PubMed  CAS  Google Scholar 

  43. Doyon Y et al (2008) Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases. Nat Biotechnol 26:702–708

    Article  PubMed  CAS  Google Scholar 

  44. Pearson H (2008) Protein engineering: the fate of fingers. Nature 455:160–164

    Article  PubMed  CAS  Google Scholar 

  45. Maeder ML et al (2008) Rapid “open-source” engineering of customized zinc-finger nucleases for highly efficient gene modification. Mol Cell 31:294–301

    Article  PubMed  CAS  Google Scholar 

  46. Sander JD et al (2011) Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA). Nat Methods 8:67–69

    Article  PubMed  CAS  Google Scholar 

  47. Meyer M, de Angelis MH, Wurst W, Kuhn R (2010) Gene targeting by homologous recombination in mouse zygotes mediated by zinc-finger nucleases. Proc Natl Acad Sci USA 107:15022–15026

    Article  PubMed  CAS  Google Scholar 

  48. Miller JC et al (2011) A TALE nuclease architecture for efficient genome editing. Nat Biotechnol 29:143–148

    Article  PubMed  CAS  Google Scholar 

  49. Horn C et al (2007) Splinkerette PCR for more efficient characterization of gene trap events. Nat Genet 39:933–934

    Article  PubMed  CAS  Google Scholar 

  50. Vooijs M, Jonkers J, Berns A (2001) A highly efficient ligand-regulated Cre recombinase mouse line shows that loxP recombination is position dependent. EMBO Rep 2:292–297

    Article  PubMed  CAS  Google Scholar 

  51. Lewandoski M (2001) Conditional control of gene expression in the mouse. Nat Rev Genet 2:743–755

    Article  PubMed  CAS  Google Scholar 

  52. Brickman JM, Tsakiridis A, To C, Stanford WL (2010) A wider context for gene trap mutagenesis. Methods Enzymol 477:271–295

    Article  PubMed  CAS  Google Scholar 

  53. Friedel RH, Soriano P (2010) Gene trap mutagenesis in the mouse. Methods Enzymol 477:243–269

    Article  PubMed  CAS  Google Scholar 

  54. Lein ES et al (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature 445:168–176

    Article  PubMed  CAS  Google Scholar 

  55. Narayanan K, Chen Q (2011) Bacterial artificial chromosome mutagenesis using recombineering. J Biomed Biotechnol 2011:971296

    Article  PubMed  CAS  Google Scholar 

  56. Haruyama N, Cho A, Kulkarni A B (2009) Overview: engineering transgenic constructs and mice. Curr Protoc Cell Biol Chapter 19:Unit 19 10

    Google Scholar 

  57. Hacking DF (2008) ‘Knock, and it shall be opened’: knocking out and knocking in to reveal mechanisms of disease and novel therapies. Early Hum Dev 84:821–827

    Article  PubMed  Google Scholar 

  58. Gama Sosa MA, De Gasperi R, Elder GA (2010) Animal transgenesis: an overview. Brain Struct Funct 214:91–109

    Article  PubMed  CAS  Google Scholar 

  59. Di Domenico AI, Christodoulou I, Pells SC, McWhir J, Thomson AJ (2008) Sequential genetic modification of the hprt locus in human ESCs combining gene targeting and recombinase-mediated cassette exchange. Cloning Stem Cells 10:217–230

    Article  PubMed  CAS  Google Scholar 

  60. Heintz N, Mamounas L (2011) Gene expression nervous system ATLAS (GENSAT) project. Contract #NO1-NS-7-2370. National Institute of Neurological Disorders and Stroke. http://www.gensat.org

  61. Kaelin CB, Xu AW, Lu XY, Barsh GS (2004) Transcriptional regulation of Agouti-related protein (Agrp) in transgenic mice. Endocrinology 145:5798–5806

    Article  PubMed  CAS  Google Scholar 

  62. Helms AW et al (2005) Sequential roles for Mash1 and Ngn2 in the generation of dorsal spinal cord interneurons. Development 132: 2709–2719

    Article  PubMed  CAS  Google Scholar 

  63. Anthony TE, Klein C, Fishell G, Heintz N (2004) Radial glia serve as neuronal progenitors in all regions of the central nervous system. Neuron 41:881–890

    Article  PubMed  CAS  Google Scholar 

  64. Dragatsis I, Zeitlin S (2000) CaMKII alpha-cre transgene expression and recombination patterns in the mouse brain. Genesis 26:133–135

    Article  PubMed  CAS  Google Scholar 

  65. Minichiello L et al (1999) Essential role for TrkB receptors in hippocampus-mediated learning. Neuron 24:401–414

    Article  PubMed  CAS  Google Scholar 

  66. Boillee S et al (2006) Onset and progression in inherited ALS determined by motor neurons and microglia. Science 312:1389–1392

    Article  PubMed  CAS  Google Scholar 

  67. Eriksson B, Bergqvist I, Eriksson M, Holmberg D (2000) Functional expression of Cre recombinase in sub-regions of mouse CNS and retina. FEBS Lett 479:106–110

    Article  PubMed  CAS  Google Scholar 

  68. Zinyk DL, Mercer EH, Harris E, Anderson DJ, Joyner AL (1998) Fate mapping of the mouse midbrain-hindbrain constriction using a site-specific recombination system. Curr Biol 8:665–668

    Article  PubMed  CAS  Google Scholar 

  69. van den Bout CJ, Machon O, Rosok O, Backman M, Krauss S (2002) The mouse enhancer element D6 directs Cre recombinase activity in the neocortex and the hippocampus. Mech Dev 110:179–182

    Article  PubMed  Google Scholar 

  70. Matsushita N, Kobayashi K, Miyazaki J (2004) Fate of transient catecholaminergic cell types revealed by site-specific recombination in transgenic mice. J Neurosci Res 78:7–15

    Article  PubMed  CAS  Google Scholar 

  71. Lemberger T et al (2007) Expression of Cre recombinase in dopaminoceptive neurons. BMC Neurosci 8:4

    Article  PubMed  CAS  Google Scholar 

  72. Lee EC et al (2001) A highly efficient Escherichia coli-based chromosome engineering system adapted for recombinogenic targeting and subcloning of BAC DNA. Genomics 73:56–65

    Article  PubMed  CAS  Google Scholar 

  73. Zhuo L et al (2001) hGFAP-cre transgenic mice for manipulation of glial and neuronal function in vivo. Genesis 31:85–94

    Article  PubMed  CAS  Google Scholar 

  74. Rivkin E, Cordes SP (2008) Generation of a transgenic mouse line expressing GFP-Cre protein from a Hoxb4 neural enhancer. Genesis 46:119–124

    Article  PubMed  CAS  Google Scholar 

  75. Potter GB et al (2009) Generation of Cre-transgenic mice using Dlx1/Dlx2 enhancers and their characterization in GABAergic interneurons. Mol Cell Neurosci 40:167–186

    Article  PubMed  CAS  Google Scholar 

  76. Yamashita T et al (2006) Regulation of CaMKII by alpha 4/PP2Ac contributes to learning and memory. Brain Res 1082:1–10

    Article  PubMed  CAS  Google Scholar 

  77. Nakazawa K et al (2002) Requirement for hippocampal CA3 NMDA receptors in associative memory recall. Science 297:211–218

    Article  PubMed  CAS  Google Scholar 

  78. Yoon HY, Enquist LW, Dulac C (2005) Olfactory inputs to hypothalamic neurons controlling reproduction and fertility. Cell 123:669–682

    Article  PubMed  CAS  Google Scholar 

  79. Hisahara S et al (2000) Targeted expression of baculovirus p35 caspase inhibitor in oligodendrocytes protects mice against autoimmune-mediated demyelination. EMBO J 19: 341–348

    Article  PubMed  CAS  Google Scholar 

  80. Banares S et al (2005) Novel pan-neuronal Cre-transgenic line for conditional ablation of genes in the nervous system. Genesis 42: 6–16

    Article  PubMed  CAS  Google Scholar 

  81. Hirasawa M et al (2001) Neuron-specific expression of Cre recombinase during the late phase of brain development. Neurosci Res 40:125–132

    Article  PubMed  CAS  Google Scholar 

  82. Sauer B, Henderson N (1989) Cre-stimulated recombination at loxP-containing DNA-sequences placed into the mammalian genome. Nucleic Acids Res 17:147–161

    Article  PubMed  CAS  Google Scholar 

  83. Imai T, Suzuki M, Sakano H (2006) Odorant receptor-derived cAMP signals direct axonal targeting. Science 314:657–661

    Article  PubMed  CAS  Google Scholar 

  84. Ishii Y et al (2006) Mouse brains deficient in neuronal PDGF receptor-beta develop normally but are vulnerable to injury. J Neurochem 98:588–600

    Article  PubMed  CAS  Google Scholar 

  85. Xu Q, Tam M, Anderson SA (2008) Fate mapping nkx2.1-lineage cells in the mouse telencephalon. J Comp Neurol 506:16–29

    Article  PubMed  CAS  Google Scholar 

  86. Matsuki T et al (2009) Selective loss of GABA(B) receptors in orexin-producing neurons results in disrupted sleep/wakefulness architecture. Proc Natl Acad Sci USA 106: 4459–4464

    Article  PubMed  CAS  Google Scholar 

  87. Tanahira C et al (2009) Parvalbumin neurons in the forebrain as revealed by parvalbumin-Cre transgenic mice. Neurosci Res 63:213–223

    Article  PubMed  CAS  Google Scholar 

  88. Dhillon H et al (2006) Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron 49:191–203

    Article  PubMed  CAS  Google Scholar 

  89. Balthasar N et al (2005) Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell 123: 493–505

    Article  PubMed  CAS  Google Scholar 

  90. Zhu Y et al (2001) Ablation of NF1 function in neurons induces abnormal development of cerebral cortex and reactive gliosis in the brain. Genes Dev 15:859–876

    Article  PubMed  CAS  Google Scholar 

  91. Korets-Smith E et al (2004) Cre recombinase specificity defined by the tau locus. Genesis 40:131–138

    Article  PubMed  CAS  Google Scholar 

  92. Dewachter I et al (2002) Neuronal deficiency of presenilin 1 inhibits is amyloid plaque formation and corrects hippocampal LTP but not a cognitive defect of APP V7171 transgenic mice. Neurobiol Aging 23:511

    Google Scholar 

  93. Mitsui S, Saito M, Mori K, Yoshihara Y (2007) A transcriptional enhancer that directs telencephalon-specific transgene expression in mouse brain. Cereb Cortex 17:522–530

    Article  PubMed  Google Scholar 

  94. Sahly I et al (2007) 5-HTIA-iCre, a new transgenic mouse line for genetic analyses of the serotonergic pathway. Mol Cell Neurosci 36:27–35

    Article  PubMed  CAS  Google Scholar 

  95. Fogarty M et al (2007) Spatial genetic patterning of the embryonic neuroepithelium generates GABAergic interneuron diversity in the adult cortex. J Neurosci 27:10935–10946

    Article  PubMed  CAS  Google Scholar 

  96. Battiste J et al (2007) Ascl1 defines sequentially generated lineage-restricted neuronal and oligodendrocyte precursor cells in the spinal cord. Development 134:285–293

    Article  PubMed  CAS  Google Scholar 

  97. Kim EJ, Leung CT, Reed RR, Johnson JE (2007) In vivo analysis of Ascl1 defined progenitors reveals distinct developmental dynamics during adult neurogenesis and gliogenesis. J Neurosci 27:12764–12774

    Article  PubMed  CAS  Google Scholar 

  98. Zhu XQ et al (2011) Age-dependent fate and lineage restriction of single NG2 cells. Development 138:745–753

    Article  PubMed  CAS  Google Scholar 

  99. Lundell TG, Zhou Q, Doughty ML (2009) Neurogenin1 expression in cell lineages of the cerebellar cortex in embryonic and postnatal mice. Dev Dyn 238:3310–3325

    Article  PubMed  CAS  Google Scholar 

  100. Zirlinger M, Lo LC, McMahon J, McMahon AP, Anderson DJ (2002) Transient expression of the bHLH factor neurogenin-2 marks a subpopulation of neural crest cells biased for a sensory but not a neuronal fate. Proc Natl Acad Sci USA 99:8084–8089

    Article  PubMed  CAS  Google Scholar 

  101. Gerfen C (2011) Cre Driver Project. Transgenic mice/rats. National Institute of Mental Health. http://www.nccrdatabase.ethz.ch/

  102. Leone DP et al (2003) Tamoxifen-inducible glia-specific Cre mice for somatic mutagenesis in oligodendrocytes and Schwann cells. Mol Cell Neurosci 22:430–440

    Article  PubMed  CAS  Google Scholar 

  103. Doerflinger NH, Macklin WB, Popko B (2003) Inducible site-specific recombination in myelinating cells. Genesis 35:63–72

    Article  PubMed  CAS  Google Scholar 

  104. Weber P, Metzger D, Chambon P (2001) Temporally controlled targeted somatic mutagenesis in the mouse brain. Eur J Neurosci 14:1777–1783

    Article  PubMed  CAS  Google Scholar 

  105. The Jackson Laboratory (2011) The JAX mice database. http://www.jax.org/

  106. Kang SH, Fukaya M, Yang JK, Rothstein JD, Bergles DE (2010) NG2(+) CNS glial progenitors remain committed to the oligodendrocyte lineage in postnatal life and following neurodegeneration. neuron 68:668–681

    Article  PubMed  CAS  Google Scholar 

  107. Madisen L et al (2010) A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci 13:133–140

    Article  PubMed  CAS  Google Scholar 

  108. Zariwala HA et al (2011) Visual tuning properties of genetically identified layer 2/3 neuronal types in the primary visual cortex of Cre-transgenic mice. Front Syst Neurosci 4:162

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Caroline Siegenthaler for assembling Table 1.

Author information

Authors and Affiliations

  1. Institute for Medical Microbiology, Immunology, and Hygiene, Technische Universität München, Munich, Germany

    Jane Beil & Thorsten Buch

  2. Brain Research Institute, University of Zürich and Swiss Federal Institute of Technology Zürich, Zurich, Switzerland

    Isabelle M. Mansuy

Authors
  1. Jane Beil
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Isabelle M. Mansuy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thorsten Buch
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. School of Medicine, Department of Physiology, University of Alberta, Medical Sciences Building 7-14, Edmonton, T6G 2H7, Alberta, Canada

    Peter Nguyen

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Beil, J., Mansuy, I.M., Buch, T. (2013). Conditional Gene Targeting: A Refined Method for Genetic Studies in Neurosciences. In: Nguyen, P. (eds) Multidisciplinary Tools for Investigating Synaptic Plasticity. Neuromethods, vol 81. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-517-0_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-517-0_1

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-516-3

  • Online ISBN: 978-1-62703-517-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation