Gene Expression in Transgenic Mice Using Neural Promoters

Shigeo Okabe1

1 Tokyo Medical and Dental University, Tokyo, Japan
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 3.16
DOI:  10.1002/0471142301.ns0316s07
Online Posting Date:  May, 2001
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Abstract

In the first part of this unit, major considerations for the analysis of neural promoters in transgenic mice are discussed. Detailed protocols on the production of transgenic mice are not described in this unit. Advantages and disadvantages of the transgenic approach for analysis of neural cis‐acting elements are also presented. The concept of transient transgenic mice is then introduced; this method compensates for some disadvantages associated with the conventional transgenic approach. Finally, major factors influencing the efficiency of transgenic mouse production are discussed. The second part of the unit presents detailed information on a variety of neural‐specific cis‐acting elements that have been characterized by a transgenic approach. This information is useful both as a guide for carrying out the analysis of cis‐acting elements and as a reference for selection of promoter/enhancer elements for designing an appropriate transgenic construct.

     
 
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Table of Contents

  • Analysis of Neural Promoters Using Transgenic Mice
  • Neural Promoters Characterized Using the Transgenic Approach
  • Conclusion
  • Tables
     
 
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Materials

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Literature Cited

Literature Cited
   Aigner, L., Arber, S., Kapfhammer, J.P., Laux, T., Schneider, C., Botteri, F., Brenner, H.‐R., and Caroni, P. 1995. Overexpression of the neural growth‐associated protein GAP‐43 induces nerve sprouting in the adult nervous system of transgenic mice. Cell 83:269‐278.
   Andra, K., Abramowski, D., Duke, M., Probst, A., Wiederhold, K.H., Burki, K., Goedert, M., Sommer, B., and Staufenbiel, M. 1996. Expression of APP in transgenic mice: A comparison of neuron‐specific promoters. Neurobiol. Aging 17:183‐190.
   Ang, H.L., Carter, D.A., and Murphy, D. 1993. Neuron‐specific expression and physiological regulation of bovine vasopressin transgenes in mice. EMBO J. 12:2397‐2409.
   Araki, K., Araki, M., Miyazaki, J.‐I., and Vassalli, P. 1995. Site‐specific recombination of a transgene in fertilized eggs by transient expression of Cre recombinase. Proc. Natl. Acad. Sci. U.S.A. 92:160‐164.
   Banerjee, S.A., Hoppe, P., Brilliant, M., and Chikaraishi, D.M. 1992. 5′ flanking sequences of the rat tyrosine hydroxylase gene target accurate tissue‐specific, developmental, and transsynaptic expression in transgenic mice. J. Neurosci. 12:4460‐4467.
   Belecky‐Adams, T., Wight, D.C., Kopchick, J.J., and Parysek, L.M. 1993. Intragenic sequences are required for cell type‐specific and injury‐induced expression of the rat peripherin gene. J. Neurosci. 13:5056‐5065.
   Berrada, F., Ma, D., Michaud, J., Doucet, G., Giroux, L., and Kessous‐Elbaz, A. 1995. Neuronal expression of human immunodeficiency virus type 1 env proteins in transgenic mice: Distribution in the central nervous system and pathological alterations. J. Virol. 69:6770‐6778.
   Boyce, F.M., Beggs, A.H., Feener, C., and Kunkel, L.M. 1991. Dystrophin is transcribed in brain from a distant upstream promoter. Proc. Natl. Acad. Sci. U.S.A. 88:1276‐1280.
   Brandes, C., Plautz, J., Stanewsky, R., Jamison, C.F., Straume, M., Wood, K.V., Kay, S.A., and Hall, J.C. 1996. Novel features of drosophila period transcription revealed by real‐time luciferase reporting. Neuron 16:687‐692.
   Brenner, M., Kisseberth, W.C., Su, Y., Besnard, F., and Messing, A. 1994. GFAP promoter directs astrocyte‐specific expression in transgenic mice. J. Neurosci. 14:1030‐1037.
   Brinster, R.L., Chen, H.Y., Trumbauer, M.E., Yagle, M.K., and Palmiter, R.D. 1985. Factors affecting the efficiency of introducing foreign DNA into mice by microinjecting eggs. Proc. Natl. Acad. Sci. U.S.A. 82:4438‐4442.
   Castillo, M.B., Celio, M.R., Andressen, C., Gotzos, V., Rulicke, T., Berger, M.C., Weber, J., and Berchtold, M.W. 1995. Production and analysis of transgenic mice with ectopic expression of parvalbumin. Arch. Biochem. Biophys. 317:292‐298.
   Chada, K., Magram, J., Raphael, K., Radice, G., Lacy, E., and Costantini, F. 1985. Specific expression of a foreign beta‐globin gene in erythroid cells of transgenic mice. Nature 314:377‐380.
   Chalfie, M., Tu, Y., Euskirchen, G., Ward, W.W., and Prasher, D.C. 1994. Green fluorescent protein as a marker for gene expression. Science 263:802‐805.
   Charron, G., Guy, L.‐G., Bazinet, M., and Julien, J.‐P. 1995a. Multiple neuron‐specific enhancers in the gene coding for the human neurofilament light chain. J. Biol. Chem. 270:30604‐30610.
   Charron, G., Julien, J.‐P., and Bibor‐Hardy, V. 1995b. Neuron specificity of the neurofilament light promoter in transgenic mice requires the presence of DNA unwinding elements. J. Biol. Chem. 270:25739‐25745.
   Chatot, C.L., Lewis, J.L., Torres, I., and Ziomek, C.A. 1990. Development of 1‐cell embryos from different strains of mice in CZB medium. Biol. Reprod. 42:432‐440.
   Chen, J., Tucker, C.L., Woodford, B., Szél, A., Lem, J., Gianella‐Borradori, A., Simon, M.I., and Bogenmann, E. 1994. The human blue opsin promoter directs transgene expression in short‐wave cones and bipolar cells in the mouse retina. Proc. Natl. Acad. Sci. U.S.A. 91:2611‐2615.
   Colucci‐D'Amato, G.L., Santelli, G., D'Alessio, A., Chiappetta, G., Mineo, A., Manzo, G., Vecchio, G., and de Franciscis, V. 1995. Dbl expression driven by the neuron specific enolase promoter induces tumor formation in transgenic mice with a p53(+/−) genetic background. Biochem. Biophys. Res. Commun. 216:762‐770.
   Danciger, E., Mettling, C., Vidal, M., Morris, R., and Margolis, F. 1989. Olfactory marker protein gene: Its structure and olfactory neuron‐specific expression in transgenic mice. Proc. Natl. Acad. Sci. U.S.A. 86:8565‐8569.
   Donoghue, M.J., Alvarez, J.D., Merlie, J.P., and Sanes, J.R. 1991. Fiber type‐ and position‐dependent expression of a myosin light chain‐CAT transgene detected with a novel histochemical stain for CAT. J. Cell Biol. 115:423‐434.
   Echelard, Y., Vassileva, G., and McMahon, A.P. 1994. Cis‐acting regulatory sequences governing Wnt‐1 expression in the developing mouse CNS. Development 120:2213‐2224.
   Forss‐Petter, S., Danielson, P.E., Catsicas, S., Battenberg, E., Price, J., Nerenberg, M., and Sutcliffe, J.G. 1990. Transgenic mice expressing β‐galactosidase in mature neurons under neuron‐specific enolase promoter control. Neuron 5:187‐197.
   Games, D., Adams, D., Alessandrini, R., Barbour, R., Berthelette, P., Blackwell, C., Carr, T., Clemens, J., Donaldson, T., Gillespie, F., Guido, T., Hagopian, S., Johnson‐Wood, K., Khan, K., Lee, M., Leibowitz, P., Lieberburg, I., Little, S., Masliah, E., McConlogue, L., Montoya‐Zavala, M., Mucke, L., Paganini, L., Penniman, E., Power, M., Schenk, D., Seubert, P., Snyder, B., Soriano, F., Tan, H., Vitale, J., Wadsworth, S., Wolozin, B., and Zhao, J. 1995. Alzheimer‐type neuropathology in transgenic mice overexpressing V717F b‐amyloid precursor protein. Nature 373:523‐527.
   Gerlai, R. 1996. Gene‐targeting studies of mammalian behavior: Is it the mutation or the background genotype?Trends Neurosci. 19:177‐181.
   Gloster, A., Wu, W., Speelman, A., Weiss, S., Causing, C., Pozniak, C., Reynolds, B., Chang, E., Toma, J.G., and Miller, F.D. 1994. The Tα1 α‐tubulin promoter specifies gene expression as a function of neuronal growth and regeneration in transgenic mice. J. Neurosci. 14:7319‐7330.
   Gordon, J.W. 1993. Production of transgenic mice. Methods Enzymol. Vol 225:747‐770.
   Gorman, C.M., Moffat, L.F., and Howard, B.H. 1982. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol. Cell Biol. 2:1044‐1051.
   Gossler, A. and Zachgo, J. 1993. Gene and enhancer trap screens in ES cell chimeras. In Gene Targeting A Practical Approach (A.L. Joyner, ed.) pp. 181‐227. IRL Press, Oxford.
   Greenberg, J.M., Boehm, T., Sofroniew, M.V., Keynes, R.J., Barton, S.C., Norris, M.L., Surani, M.A., Spillantini, M.‐G., and Rabbitts, T.H. 1990. Segmental and developmental regulation of a presumptive T‐cell oncogene in the central nervous system. Nature. 344:158‐160.
   Gu, M., Marth, J.D., Orban, P.C., Mossmann, H., and Rajewsky, K. 1994. Deletion of a DNA polymerase b gene segment in T cells using cell type‐specific gene targeting. Science. 265:103‐106.
   Halliday, A. and Cepko, C.L. 1992. Generation and migration of cells in the developing striatum. Neuron. 9:15‐26.
   Hogan, B., Beddington, R., Costantini, F., and Lacy, E. 1994. Manipulating the mouse embryo—A laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
   Hoyle, G.W., Mercer, E.H., Palmiter, R.D., and Brinster, R.L. 1994. Cell‐specific expression from the human dopamine beta‐hydroxylase promoter in transgenic mice is controlled via a combination of positive and negative regulatory elements. J. Neurosci. 14:2455‐2463.
   Ikawa, M., Kominami, K., Yoshimura, Y., Tanaka, K., Nishimune, Y., and Okabe, M. 1995. Green fluorescent protein as a marker in transgenic mice. Develop. Growth Differ. 37:455‐459.
   Kammesheidt, A., Boyce, F.M., Spanoyannis, A.F., Cummings, B.J., Ortegón, M., Cotman, C., Vaught, J.L., and Neve, R.L. 1992. Deposition of b/A4 immunoreactivity and neuronal pathology in transgenic mice expressing the carboxyl‐terminal fragment of the Alzheimer amyloid precursor in the brain. Proc. Natl. Acad. Sci. U.S.A. 89:10857‐10861.
   Kaneda, N., Sasaoka, T., Kobayashi, K., Kiuchi, K., Nagatsu, I., Kurosawa, Y., Fujita, K., Yokoyama, M., Nomura, T., Katsuki, M., and Nagatsu, T. 1991. Tissue‐specific and high‐level expression of the human tyrosine hydroxylase gene in transgenic mice. Neuron. 6:583‐594.
   Kapur, R.P., Hoyle, G.W., Mercer, E.H., Brinster, R.L., and Palmiter, R.D. 1991. Some neuronal cell populations express human dopamine b‐hydroxylase‐lacZ transgenes transiently during embryonic development. Neuron 7:717‐727.
   Lardelli, M., Williams, R., Mitsiadis, T., and Lendahl, U. 1996. Expression of the Notch 3 intracellular domain in mouse central nervous system progenitor cells is lethal and leads to disturbed neural tube development. Mech. Dev. 59:177‐190.
   Lem, J., Applebury, M.L., Falk, J.D., Flannery, J.G., and Simon, M.I. 1991. Tissue‐specific and developmental regulation of rod opsin chimeric genes in transgenic mice. Neuron 6:201‐210.
   Mann, J.R. and McMahon, A.P. 1993. Factors influencing production frequency of transgenic mice. Methods Enzymol. Vol 225:771‐781.
   Martinou, J.‐C., Dubois‐Dauphin, M., Staple, J.K., Rodriguez, I., Frankowski, H., Missotten, M., Albertini, P., Talabot, D., Catsicas, S., Pietra, C., and Huarte, J. 1994. Overexpression of BCL‐2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron 13:1017‐1030.
   Matsuo, K., Ikeshima, H., Shimoda, K., Umezawa, A., Hata, J., Maejima, K., Nojima, H., and Takano, T. 1993. Expression of the rat calmodulin gene II in the central nervous system: A 294‐base promoter and 68‐base leader segment mediates neuron‐specific gene expression in transgenic mice. Brain Res. Mol. Brain Res. 20:9‐20.
   Mayford, M., Wang, J., Kandel, E.R., and O'Dell, T.J. 1995. CaMKII regulates the frequency‐response function of hippocampal synapses for the production of both LTD and LTP. Cell 81:891‐904.
   Mayford, M., Bach, M.E., Huang, Y.‐Y., Wang, L., Hawkins, R.D., and Kandel, E.R. 1996a. Control of memory formation through regulated expression of a CaMKII transgene. Science 274:1678‐1683.
   Mayford, M., Baranes, D., Podsypanina, K., and Kandel, E.R. 1996b. The 3′‐untranslated region of CaMKIIa is a cis‐acting signal for the localization and translation of mRNA in dendrites. Proc. Natl. Acad. Sci. U.S.A. 93:13250‐13255.
   Mercer, E.H., Hoyle, G.W., Kapur, R.P., Brinster, R.L., and Palmiter, R.D. 1991. The dopamine beta‐hydroxylase gene promoter directs expression of E. coli lacZ to sympathetic and other neurons in adult transgenic mice. Neuron 7:703‐716.
   Messing, A., Behringer, R.R., Hammang, J.P., Palmiter, R.D., Brinster, R.L., and Lemke, G. 1992. P0 promoter directs expression of reporter and toxin genes to Schwann cells of transgenic mice. Neuron 8:507‐520.
   Millar, A.J., Short, S.R., Chua, N.‐H., and Kay, S.A. 1992. A novel circadian phenotype based on firefly luciferase expression in transgenic plants. Plant Cell 4:1075‐1087.
   Morita, S., Kobayashi, K., Mizuguchi, T., Yamada, K., Nagatsu, I., Titani, K., Fujita, K., Hidaka, H., and Nagatsu, T. 1993. The 5′‐flanking region of the human dopamine beta‐hydroxylase gene promotes neuron subtype‐specific gene expression in the central nervous system of transgenic mice. Brain Res. Mol. Brain Res. 17:239‐244.
   Niwa, H., Yamamura, K.‐I., and Miyazaki, J.‐I. 1991. Efficient selection of high‐expression transfectants with a novel eukaryotic vector. Gene 108:193‐200.
   Oberdick, J., Smeyne, R.J., Mann, J.R., Zackson, S., and Morgan, J.I. 1990. A promoter that drives transgene expression in cerebellar Purkinje and retinal bipolar neurons. Science 248:223‐226.
   Patil, N., Lacy, E., and Chao, M.V. 1990. Specific neuronal expression of human NGF receptors in the basal forebrain and cerebellum of transgenic mice. Neuron 2:437‐447.
   Ponte, I., Martinez, P., Ramirez, A., Jorcano, J.L., Monzo, M., and Suau, P. 1994. Transcriptional activation of histone H1 zero during neuronal terminal differentiation. Brain Res. Dev. Brain Res. 80:35‐44.
   Prasher, D.C. 1995. Using GFP to see the light. Trends Genet. 11:320‐323.
   Quon, D., Wang, Y., Catalano, R., Scardina, J.M., Murakami, K., and Cordell, B. 1991. Formation of b‐amyloid protein deposits in brains of transgenic mice. Nature 352:239‐241.
   Rincón‐Limas, D.E., Geske, R.S., Xue, J.‐J., Hsu, C.Y., Overbeek, P.A., and Patel, P.I. 1994. 5′‐flanking sequences of the human HPRT gene direct neuronal expression in the brain of transgenic mice. J. Neurosci. Res. 38:259‐267.
   Robertson, L.M., Kerppola, T.K., Vendrell, M., Luk, D., Smeyne, R.J., Bocchiaro, C., Morgan, J.I., and Curran, T. 1995. Regulation of c‐fos expression in transgenic mice requires multiple interdependent transcription control elements. Neuron 14:241‐252.
   Roderick, T.H. and Guidi, J.H. 1989. Strain distribution of polymorphic variants. In Genetic Variants and Strains of the Laboratory Mouse (M.F. Lyon and A.G. Searle, eds.) pp. 663‐772. Oxford University Press, Oxford.
   Sanes, J.R., Rubenstein, J.L.R., and Nicolas, J.‐F. 1986. Use of a recombinant retrovirus to study post‐implantation cell lineage in mouse embryos. EMBO J. 5:3133‐3142.
   Santerre, R.F., Bales, K.R., Janney, M.J., Hannon, K., Fisher, L.F., Bailey, C.S., Morris, J., Ivarie, R., and II, C.K.S. 1993. Expression of bovine myf5 induces ectopic skeletal muscle formation in transgenic mice. Mol. Cell. Biol. 13:6044‐6051.
   Sasahara, M., Fries, J.W.U., Raines, E.W., Gown, A.M., Westrum, L.E., Frosch, M.P., Bonthron, D.T., Ross, R., and Collins, T. 1991. PDGF B‐chain in neurons of the central nervous system, posterior pituitary, and in a transgenic model. Cell 64:217‐227.
   Sasaoka, T., Kobayashi, K., Nagatsu, I., Takahashi, R., Kimura, M., Yokoyama, M., Nomura, T., Katsuki, M., and Nagatsu, T. 1992. Analysis of the human tyrosine hydroxylase promoter‐chloramphenicol acetyltransferase chimeric gene expression in transgenic mice. Brain Res. Mol. Brain Res. 16:274‐286.
   Shimoda, K., Ikeshima, H., Matsuo, K., Hata, J., Maejima, K., and Takano, T. 1995. Spatial and temporal regulation of the rat calmodulin gene III directed by a 877‐base promoter and 103‐base leader segment in the mature and embryonal central nervous system of transgenic mice. Brain Res. Mol. Brain Res. 31:61‐70.
   Taketo, M., Schroeder, A.C., Mobraaten, L.E., Gunning, K.B., Harten, G., Fox, R.R., Roderick, T.H., Stewart, C.L., Lilly, F., Hansen, C.T., and Overbeek, P.A. 1991. FVB/N: An inbred mouse strain preferable for transgenic analyses. Proc. Natl. Acad. Sci. U.S.A. 88:2065‐2069.
   Timmusk, T., Lendahl, U., Funakoshi, H., Arenas, E., Persson, H., and Metsis, M. 1995. Identification of brain‐derived neurotrophic factor promoter regions mediating tissue‐specific axotomy‐, and neuronal activity‐induced expression in transgenic mice. J. Cell Biol. 128:185‐199.
   Toggas, S.M., Masliah, E., Rockenstein, E.M., Rall, G.F., Abraham, C.R., and Mucke, L. 1994. Central nervous system damage produced by expression of the HIV‐1 coat protein gp120 in transgenic mice. Nature 367:188‐193.
   Toth, M., Ding, D., and Shenk, T. 1994. The 5′ flanking region of the serotonin 2 receptor gene directs brain specific expression in transgenic animals. Brain Res. Mol. Brain Res. 27:315‐319.
   Townes, T.M., Lingrel, J.B., Brinster, R.L., and Palmiter, R.D. 1985. Erythroid specific expression of human beta‐globin genes in transgenic mice. EMBO J. 4:1715‐1723.
   Tsien, J.Z., Chen, D.F., Gerber, D., Tom, C., Mercer, E.H., Anderson, D.J., Mayford, M., Kandel, E.R., and Tonegawa, S. 1996. Subregion‐ and cell type‐restricted gene knockout in mouse brain. Cell 87:1317‐1326.
   Vandaele, S., Nordquist, D.T., Feddersen, R.M., Tretjakoff, I., Peterson, A.C., and Orr, H.T. 1991. Purkinje cell protein‐2 regulatory regions and transgene expression in cerebellar compartments. Genes Dev. 5:1136‐1148.
   Vanselow, J., Grabczyk, E., Ping, J., Baetscher, M., Teng, S., and Fishman, M.C. 1994. GAP‐43 transgenic mice: Dispersed genomic sequences confer a GAP‐43‐like expression pattern during development and regeneration. J. Neurosci. 14:499‐510.
   Vidal, M., Morris, R., Grosveld, F., and Spanopoulou, E. 1990. Tissue‐specific control elements of the Thy‐1 gene. EMBO J. 9:833‐840.
   Wang, Y., Macke, J.P., Merbs, S.L., Zack, D.J., Klaunberg, B., Bennett, J., Gearhart, J., and Nathans, J. 1992. A locus control region adjacent to the human red and green visual pigment genes. Neuron 9:429‐440.
   Whitten, W.K. and Biggers, J.D. 1968. Complete development in vitro of the pre‐implantation stages of the mouse in a simple chemically defined medium. J. Reprod. Fert. 17:399‐401.
   Wirak, D.O., Bayney, R., Kundel, C.A., Lee, A., Scangos, G.A., Trapp, B.D., and Unterbeck, A.J. 1991a. Regulatory region of human amyloid precursor protein (APP) gene promotes neuron‐specific gene expression in the CNS of transgenic mice. EMBO J. 10:289‐296.
   Wirak, D.O., Bayney, R., Ramabhadran, T.V., Fracasso, R.P., Hart, J.T., Hauer, P.E., Hsiau, P., Pekar, S.K., Scangos, G.A., Trapp, B.D., and Unterbeck, A.J. 1991b. Deposits of amyloid b protein in the central nervous system of transgenic mice. Science 253:323‐325.
   Wood, K.V. 1995. Marker proteins for gene expression. Curr. Opin. Biotech. 6:50‐58.
   Wuenschell, C.W., Mori, N., and Anderson, D.J. 1990. Analysis of SCG10 gene expression in transgenic mice reveals that neural specificity is achieved through selective derepression. Neuron 4:595‐602.
   Xu, Z., Cork, L.C., Griffin, J.W., and Cleveland, D.W. 1993. Increased expression of neurofilament subunit NF‐L produces morphological alterations that resemble the pathology of human motor neuron disease. Cell 73:23‐33.
   Zack, D.J., Bennett, J., Wang, Y., Davenport, C., Klaunberg, B., Gearhart, J., and Nathans, J. 1991. Unusual topography of bovine rhodopsin promoter‐lacZ fusion gene expression in transgenic mouse retinas. Neuron 6:187‐199.
   Zimmerman, L., Lendahl, U., Cunningham, M., McKay, R., Parr, B., Gavin, B., Mann, J., Vassileva, G., and McMahon, A. 1994. Independent regulatory elements in the nestin gene direct transgene expression to neural stem cell or muscle precursors. Neuron 12:11‐24.
Key Reference
   Hogan et al., 1994. See above.
  The best reference for the production of transgenic mice.
   Vidal et al., 1990; Zimmerman et al., 1994
  Two good examples for the promoter/enhancer analyses using different strategies.
Internet Resources
  http://www.gdb.org/Dan/tbase/tbase.html
  Web site for the database of transgenic/knockout mice. This site also has links to a variety of related Web sites.
  http://www.informatics.jax.org/mgd.html
  Web site for mouse genome database at Jackson Laboratory.
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