Abstract
The introduction of cloned genes into cells has greatly increased our knowledge of the factors that regulate the transcription of these genes and of the function of the proteins that they encode. Recently, techniques have been developed that allow the incorporation of cloned genes into the germline of mice (Gordon et al., 1980 9; Brinster et al., 1981 3; Costantini and Lacy, 1981 7). The generation of such transgenic animals has advanced our understanding of the elements involved in regulating tissue specificity and developmental expression of the incorporated genes. Additionally, these studies have yielded insight into the involvement of the transgenes in the physiology of the animal (Palmiter and Brinster, 1986 24). The application of this technique to genes of neurobiological interest can provide insights into the role specific genes play in the organization and function of the mammalian nervous system. In this article, we provide an overall view of the various aspects involved in generating transgenic animals and some of the potential applications of the technique to genes of neurobiological importance.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Adams J. M., Harris A. W., Pinkert C. A., Corcoran L. M., Alexander W. S., Cory S., Palmiter R. D., and Brinster R. L. (1985) The c-Myc oncogene driven by immunoglobin enhancers induces lymphoid malignancy in transgenic mice. Nature (Lond.) 318, 533–538.
Alt F. W., Blackwell T. K., and Yancopoulos G D. (1987) Development of primary antibody repertoire. Science 238, 1079–1081.
Brinster R. L., Chen H. Y., Trumbauer M. E., Senear A. W., and Warren R., and Palmiter R. D. (1981) Somatic expression of herpes thymidine kinase in mice following injection of a fusion gene into eggs. Cell 27, 223–231.
Brinster R. L., Chen H. Y., Messing A., van Dyke T., Levine A. J., and Palmiter R. D. (1984) Transgenic mice harboring SV40 T-antigen genes develop characteristic brain tumors. Cell 37, 367–379
Brmster 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. USA 82, 4438–4442.
Chada K., Magram J., Raphael K., Radice G., Lacy E., and Costantini F. (1985) Specific expresion of a foreign β-globin in erythroid cells of transgenic mice. Nature (Lond.) 314, 377–380.
Costantini F. and Lacy E. (1981) Indroduction of a rabbit β-globin gene into the mouse germ-line. Nature (Lond.) 294, 92–94
Doetschman T., Gregg R. G., Maeda N., Hooper M L., Melton D. W., Thompson S., and Smithies O. (1987) Targeted correction of a mutant HPRT gene in mouse embryonic stem cells. Nature (Lond.) 330, 576–578.
Gordon J. W., Scangos G. A., Plotkin D. J., Barbosa J. A., and Ruddle F. H. (1980) Genetic transformation of mouse embryos by micoinjection of purified DNA. Proc. Natl. Acad. Sci. USA 77, 7380–7384.
Hammer R. E., Krumlauf R., Camper S. A., Brinster R. L., and Tilghman S. M. (1987) Diversity of alpha-fetoprotein gene expression in mice is generated by a combination of separate enhancer elements. Science 235, 53–58.
Hanahan D. (1985) Heritable formation of pancreatic β-cell tumors in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes. Nature (Lond.) 315, 115–122.
Herskowitz I. (1987) Functional inactivation of genes by dominant negative mutations. Nature (Lond.) 329, 219–222.
Hogan B., Costantini F., and Lacy E. (1986) Manipulating the Mouse Embryo (Cold Spring Harbor Laboratory, New York, NY).
Hooper M., Hardy K., Handyside A., Hunter S.; and Monk M. (1987) HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germ-line colonization by cultured cells. Nature (Lond.) 326, 292–295.
Izant J. G. and Weintraub H. (1985) Constitutive and conditional suppression of exogenous and endogenous genes by anti-sense RNA. Science 229, 345–352.
Jaenisch R. (1976) Germ line integratin and Mendelian transmission of the exogenous Moloney leukemia virus. Proc. Natl. Acad. Sci. USA 73, 1260–1264.
Kim S. and Wold B.J. (1985) Stable reduction of thymidine kinase activity in cells expressing high levels of anti-sense RNA. Cell 42, 129–138.
Kuehn M. R., Bradley A., Robertson E. J., and Evans M. J. (1987). A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT− mutations ito mice. Nature (Lond.) 326, 295–298.
Mahon K. A., Chepelinsky A. B., Khillan J. S., Overbeck P. A., Piatigorsky J., and Westphal H. (1987) Oncogenesis of the lens in trangenic mice. Science 235, 1622–1628.
Martin G. R. (1980) Teratocarcinomas and mammalian embryogenesis. Science 209, 768–775.
Mason A. J., Pitts S. L., Nikolics K., Szonyi E., Wilcox J. N., Seeburg P. H., and Stewart T. A. (1986) The hypogonadal mouse: Reproductive functions restored by gene therapy. Science 234, 1372–1378.
Messing A., Chen H. Y., Palmiter R. D., and Brinster R. L. (1985) Peripheral neuropathies, hepatocellular carcinomas and islet cell adenomas in transgenic mice. Nature (Lond.) 316, 461–463.
Nelson P. L. (1977) Neuron Cell Lines, in Cell, Tissue and Organ Cultures in Neurobiology (Federoff S. and Hertz L, eds.), Academic Press, New York, pp. 347–365.
Palmiter R. D. and Brinster R. L. (1986) Germ-line transformation of mice. Ann. Rev. Genet. 20, 465–499.
Palmiter R. D., Behringer R. R., Quaife C. J., Maxwell F., Maxwell I. H., and Brinster R. L. (1987) Cell lineage ablation in transgenic mice by cell-specific expression of a toxin gene. Cell 50, 435–443.
Palmiter R. D., Chen H. Y., Messing A., and Brinster R. L. (1985) SV40 enhancer and large T-antigen are instrumental in development of choroid plexus tumors in transgenic mice. Nature (Lond.) 316, 457–460.
Pfeiffer S. E., Betschart B., Cook J., Mancini P., and Morris R. (1977) Glial Cell Lines, in Cell, Tissue, and Organ Cultures in Neurobiology (Federoff S. and Hertz L., eds.) Academic Press, New York, pp. 287–346.
Popko B., Puckett C., Lai E., Shine H. D., Readhead C., Takahashi N., Hunt S. W., Sidman R. L., and Hood L. (1987) Myelin-deficient mice: Expression of myelin basic protein and generation of mice with varying levels of myelin. Cell 48, 713–721.
Prockup D. J. (1984) Osteogenesis imperfecta: phenotypic heterogeneity, protein suicide, short and long collagen. Am. J. Hum. Genet. 36, 499–505.
Readhead C., Popko B., Takahashi M., Shine H. D., Saavedra R. A., Sidman R. L., and Hood L. (1987) Expression of myelin basic protein gene in transgenic shiverer mice: Corrections of the dysmyelinating phenotype. Cell 48, 703–712.
Robertson E., Bradley A., Kuehn M., and Evans M. (1986) Germ-line transmission of genes introduced into cultured pluripotential cells by retroviral vector. Nature (Land.) 323, 445–448.
Small J., Scangos G. A., Cork L., Jay G., and Khoury G. (1986a) The early region of human papovavirus JC induces dysmyelination in transgenic mice. Cell 46, 13–18.
Small J. A., Khoury G., Jay G., Howley P. M., and Scangos G. A. (1986b) Early regions of JC virus and BK virus induce distinct and tissue-specific tumors in transgenic mice. Proc. Natl. Acad. Sci. USA 83, 8288–8292.
Smithies O., Gregg R. G., Boggs S. S., Koralewski M. A., and Kucherlapati R. S. (1985) Insertion of DNA sequences into the human chromosomal β-globin locus by homologous recombination. Nature (Lond.) 317, 230–234.
Soriano P., Cone R. D., Mulligan R. C, and Jaenisch R. (1986) Tissue-specific and ectopic expression of genes introduced into transgenic mice by retroviruses. Science 234, 1409–1413.
Stewart T. A., Pattengale K., and Leder P. (1984) Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes. Cell 38, 627–637.
Thomas K. R. and Capecchi M. R. (1987) Site-directed mutagenesis by gene targeting in mouse embryo derived stem cells. Cell 51, 503–512.
Townes T. M., Chen H. Y., Lingrel J. B., Palmiter R. D., and Brinster R. L. (1985) Expression of human β-globin genes in transgenic mice: effects of a flanking metallothionein-human growth hormone fusion gene. Mol. Cell. Biol. 5, 1977–1983.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1990 The Humana Press Inc
About this protocol
Cite this protocol
Popko, B., Readhead, C., Dausman, J., Hood, L. (1990). Transgenic Mice in Neurobiological Research. In: Boulton, A.A., Baker, G.B., Campagnoni, A.T. (eds) Molecular Neurobiological Techniques. Neuromethods, vol 16. Humana Press. https://doi.org/10.1385/0-89603-140-3:221
Download citation
DOI: https://doi.org/10.1385/0-89603-140-3:221
Publisher Name: Humana Press
Print ISBN: 978-0-89603-140-1
Online ISBN: 978-1-59259-621-8
eBook Packages: Springer Protocols