Transgenic Mouse: Methods and Protocols

394 Pages·2002·2.558 MB·English

by  Marten H. Hofker (auth.), Marten H. Hofker, Jan van Deursen (eds.)

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Transgenic Mouse Methods and Protocols
M E T H O D S I N M O L E C U L A R B I O L O G YTM
John M. Walker, S E
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217. Neurogenetics: Methods and Protocols, edited by Nicholas 188. Epithelial Cell Culture Protocols, edited by Clare Wise, 2002
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216. PCR Detection of Microbial Pathogens: Methods and Pro- Theophilus and Ralph Rapley, 2002
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212. Single Nucleotide Polymorphisms: Methods and Protocols, byBarry W. Hicks, 2002
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211. Protein Sequencing Protocols, 2nd ed., edited by Bryan John Braman, 2002
Smith, 2003 181.Genomic Imprinting: Methods and Protocols, edited by
210. MHC Protocols, edited by Stephen H. Powis and Robert W. Andrew Ward, 2002
Vaughan, 2003 180. Transgenesis Techniques, 2nd ed.: Principles and Protocols,
209. Transgenic Mouse Methods and Protocols, edited by Marten edited by Alan R. Clarke, 2002
Hofker and Jan van Deursen, 2002 179. Gene Probes: Principles and Protocols, edited by Marilena
208. Peptide Nucleic Acids: Methods and Protocols, edited by Aquino de Muro and Ralph Rapley, 2002
Peter E. Nielsen, 2002 178. Antibody Phage Display: Methods and Protocols, edited by
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206. Endothelin Protocols, edited by Janet J. Maguire and Anthony N. MacDonald, 2001
P. Davenport, 2002 176. Steroid Receptor Methods: Protocols and Assays, edited by
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M E T H O D S I N M O L E C U L A R B I O L O G YTM
Transgenic Mouse
Methods and Protocols
Edited by
Marten H. Hofker
Department of Molecular Genetics
University of Maastricht
Maastricht, The Netherlands
Jan van Deursen
Department of Pediatrics and Adolescent Medicine
Mayo Clinic, Rochester, MN
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Library of Congress Cataloging-in-Publication Data
Transgenic mouse methods and protocols / edited by Marten H. Hofker, Jan van Deursen.
p. cm. -- (Methods in molecular biology ; 209)
Includes bibliographical references and index.
ISBN 0-89603-915-3 (alk. paper)
1. Transgenic mice--Laboratory manuals. I. Hofker, Marten H. II. Deursen, Jan van, 1930– III. Methods
in molecular biology (Totowa, N.J.) ; v. 209
QH442.6 .T724 2002
616'.93--dc21
2002068581
Preface
Mice play an important role in biomedical research. Genetically, the mouse
is very similar to the human species, and most human genes are conserved in the
mouse. Moreover, the arrangement of genes on chromosomes is similar in humans
and mice. Mouse models have been established for a wide variety of human
disorders including cancer, cardiovascular diseases, and behavioral disorders.
Transgenic Mouse Methods and Protocols covers the production and analysis of
transgenic and knockout mice. The book also includes a review of mouse models
for a wide range of genetic aberrations associated with human disease.
Many researchers played a crucial role in developing mouse technology to
the excellent state of art that has now been achieved. Landmarks include the
generation of (i) transgenic mice, (ii) pluripotent embryonic stem (ES) cell cultures,
(iii) gene knockout mice, (iv) tissue-specific knockouts, and (v) systems for
inducible gene expression mice. Most of these landmarks have not been achieved
in other mammalian systems with a comparable efficiency. In part, this is attributable
to the availability of hundreds of different inbred mouse strains, which allowed
researchers to choose from a wide range of strains while establishing these
technologies.
Transgenic Mouse Methods and Protocols has essentially the same format
as previous volumes of the series Methods in Molecular Biology. Since mouse
technology offers a wide range of possibilities, most chapters will provide the
rationale for choosing the given protocol, which is then described in step-by-step
detail. In addition, two chapters will describe alternative strategies for studying
gene function in the mouse, i.e., random mutagenesis and viral gene transduction.
The book can be roughly divided into three topics: a general introduction describing
how to deal with mice and how to generate transgenics; a technology part where
new methods will be presented, including conditional and induced knockout and
transgenic mice; and the final chapters, which highlight working with mice in
several major research areas, including cancer, immunology, and atherosclerosis.
We would like to thank the authors for their excellent contributions and Wilma
Claessen for editorial assistance. We are very grateful to Be Wieringa, Anton Berns,
and Robin Lovell Badge for leading us into the world of gene-targeting and ES
cell technology.
Marten Hofker
Jan van Deursen
v

Contents
Preface .............................................................................................................v
Contributors .....................................................................................................ix
Color Plates ................................................................................................... xiii
1 Introduction: The Use of Transgenic Mice in Biomedical Research
Marten H. Hofker....................................................................................1
2 Genetic Modification of the Mouse:
General Technology; Pronuclear and Blastocyst Injection
J. Willem Voncken.................................................................................9
3 In Vitro Fertilization/Cryopreservation
ˆ
Susan Marschall 0and Martin Hrabe de Angelis.............................35
4 Transgene Design
J. Willem Voncken...............................................................................51
5 Generating Conditional Mouse Mutants
via Tetracycline-Controlled Gene Expression
Kai Schönig and Hermann Bujard.....................................................69
6 Manipulating Large Insert Clones for Transgenesis
Sally P. A. McCormick, Catherine Y. Y. Liu, Stephen G. Young,
and Lars B. Nielsen.......................................................................105
7 Reporter Molecules in Genetically Engineered Mice
Thomas L. Saunders.........................................................................125
8 Gene Targeting in Mouse Embryonic Stem Cells
Jan van Deursen................................................................................145
9 Conditional Knockout Mice
Ralf Kühn and Frieder Schwenk......................................................159
10 Knockin Approaches
Anton J. M. Roebroek, Xiaosheng Wu, and Richard J. Bram......187
11 Aggregation of Embryos and Embryonic Stem Cells
Ronald Maatman, Marina Gertsenstein, Emile de Meijer,
Andras Nagy, and Kristina Vintersten........................................201
12 Andenovirus-Mediated Gene Transfer
Ko Willems van Dijk, Kyriakos E. Kypreos,
Christine d’Oliveira, and Frits J. Fallaux....................................231
vii
viii Contents
13 Random ENU Mutagenesis
Dian Soewarto, Véronique Blanquet,
ˆ
and Martin Hrabe de Angelis.......................................................249
14 Autopsy and Histologic Analysis of the Transgenic Mouse
Marion J. J. Gijbels and Menno P. J. de Winther..........................267
15 Bone Marrow Transplantations to Study Gene Function
in Hematopoietic Cells
Menno P. J. de Winther and Peter Heeringa..................................281
16 Quantification of Atherosclerosis in Mice
Alan Daugherty and Stewart C. Whitman.......................................293
17 Genetically Modified Mice in Cancer Research
David A. Largaespada.......................................................................311
18 Neuropathobiology in Transgenic Mice:
The Case of Alzheimer’s Disease
Jo Van Dorpe, Kurt Spittaels, Chris Van den Haute,
Ilse Dewachter, Dieder Moechars, Hugo Geerts,
and Fred Van Leuven....................................................................333
Index ............................................................................................................363
Contributors
V B • GSF Research Centre for Environment and Health,
ÉRONIQUE LANQUET
Institute of Experimental Genetics, Neuherberg, Germany
R J. B • Department of Pediatrics and Adolescent Medicine, Mayo
ICHARD RAM
Clinic, Rochester, MN
H B • Zentrum für Molekulare Biologie der Universität
ERMANN UJARD
Heidelberg (ZMBH), Heidelberg, Germany
A D • Gill Heart Institute, Division of Cardiovascular
LAN AUGHERTY
Medicine, University of Kentucky, Lexington KY
J D • Department of Pediatrics and Adolescent Medicine,
AN VAN EURSEN
Mayo Clinic, Rochester, MN
I D • Experimental Genetics Group, Center for Human
LSE EWACHTER
Genetics, Flemish Institute for Biotechnology, Katholieke Universiteit
Leuven, Leuven, Belgium
K W D • Departments of General Internal Medicine and of
O ILLEMS VAN IJK
Human Genetics, Leiden University Medical Center, Leiden, The
Netherlands
J V D • Experimental Genetics Group, Center for Human
O AN ORPE
Genetics, Flemish Institute for Biotechnology, Katholieke Universiteit
Leuven, Leuven, Belgium
F J. F • Department of Human Genetics, Leiden University
RITS ALLAUX
Medical Center, Leiden, The Netherlands
H G • Janssen Research Foundation, Beerse, Belgium
UGO EERTS
M G • Samuel Lunenfeld Research Institute, Mount Sinai
ARINA ERTSENSTEIN
Hospital, Toronto, Canada
M J. J. G • Department of Molecular Genetics, Universiteit
ARION IJBELS
Maastricht, Maastricht, The Netherlands
C V H • Experimental Genetics Group, Center for Human
HRIS AN DEN AUTE
Genetics, Flemish Institute for Biotechnology, Katholieke Universiteit
Leuven, Leuven, Belgium
P H • Department of Clinical and Experimental Immunology,
ETER EERINGA
Universiteit Maastricht, Maastricht, The Netherlands
M H. H • Department of Molecular Genetics, Universiteit
ARTEN OFKER
Maastricht, Maastricht, The Netherlands
ˆ
M H A • GSF Research Centre for Environment and
ARTIN RABE DE NGELIS
Health, Institute of Experimental Genetics, Neuherberg, Germany
R K • Artemis Pharmaceuticals GmbH, Cologne, Germany
ALF ÜHN
ix