Transgenic Animal Technology. A Laboratory Handbook

683 Pages·2014·39.19 MB·English

by  Carl A. Pinkert (Auth.)

Transgenic Animal Technology
Transgenic Animal
Technology
A Laboratory Handbook
Third Edition
Edited by
Carl A. Pinkert
The University of Alabama
Tuscaloosa, AL, USA
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List of Contributors
Satoshi Akagi Animal Breeding and Reproduction Research Division, Institute
of Livestock and Grassland Science, National Agriculture and Food Research
Organization,Tsukuba,Ibaraki,Japan
Anna V. Anagnostopoulos Mouse Genome Informatics, The Jackson Laboratory,
BarHarbor,ME
Benjamin P. Beaton Division of Animal Sciences, University of Missouri,
Columbia,MO
CoryF.Brayton JohnsHopkinsUniversity,Baltimore,MD
SteveBrown MRCMammalianGeneticsUnit,Harwell,Oxford,UK
Anthony W.S. Chan Yerkes National Primate Research Center, Department of
Human Genetics, Department of Pediatrics, Emory University School of Medicine,
EmoryUniversity,Atlanta,GA
TomDoetschman UniversityofArizona,Tucson,AZ
Rex A. Dunham School of Fisheries, Aquaculture, and Aquatic Sciences, Auburn
University,Auburn,AL
David A. Dunn Department of Biological Sciences, State University of New York
atOswego,Oswego,NY
Janan T. Eppig Mouse Genome Informatics, The Jackson Laboratory, Bar
Harbor,ME
Almudena Ferna´ndez National Centre for Biotechnology (CNB-CSIC),
DepartmentofMolecularandCellularBiology,Madrid,Spain
Tatiana Flisikowska Livestock Biotechnology, Technische Universita¨t Mu¨nchen,
Freising,Germany
xiv ListofContributors
Vasiliy Galat Department of Pediatrics, Northwestern University Medical School
and Developmental Biology Program, Ann & Robert H. Lurie Children’s Hospital
ofChicagoResearchCenter,Chicago,IL
Robert A. Godke Embryo Biotechnology Laboratory, Department of Animal
Science,LouisianaStateUniversity,BatonRouge,LA
Philip Iannaccone Department of Pediatrics, Northwestern University Medical
School and Developmental Biology Program, Ann & Robert H. Lurie Children’s
HospitalofChicagoResearchCenter,Chicago,IL
Michael H. Irwin Department of Pathobiology, College of Veterinary Medicine,
AuburnUniversity,Auburn,AL
Larry W. Johnson Department of Genetics, The University of Alabama at
Birmingham,Birmingham,AL
Yoko Kato Laboratory of Animal Reproduction, College of Agriculture, Kinki
University,Nakamachi,Nara,Japan
Teoan Kim Department of Physiology, Catholic University of Daegu School of
Medicine,Daegu,RepublicofKorea
Alexander Kind Livestock Biotechnology, Technische Universita¨t Mu¨nchen,
Freising,Germany
BonChulKoo DepartmentofPhysiology,CatholicUniversityofDaeguSchoolof
Medicine,Daegu,RepublicofKorea
Mo Sun Kwon Department of Physiology, Catholic University of Daegu School
ofMedicine,Daegu,RepublicofKorea
DanielJ.Ledbetter DepartmentofBiology,UniversityofKentucky,Lexington,KY
MichaelJ.Martin SpringPointProject,Minneapolis,MN
Kazutsugu Matsukawa Multidisciplinary Science Cluster, Life and Environmental
MedicineScienceUnit,KochiUniversity,Nankoku,Kochi,Kerala,India
Colin McKerlie The Hospital for Sick Children and University of Toronto,
Toronto,ON,Canada
Llu´ıs Montoliu National Centre for Biotechnology (CNB-CSIC), Department of
MolecularandCellularBiology,Madrid,Spain
ListofContributors xv
Paul E. Mozdziak Prestage Department of Poultry Science College of Agriculture
andLifeSciencesNorthCarolinaStateUniversityRaleigh,NCUSA
Akira Onishi Transgenic Pig Research Unit, Genetically Modified Organism
ResearchCenter,NationalInstituteofAgrobiologicalSciences,Tsukuba,Ibaraki,Japan
PaulA. Overbeek Department of Molecular and Cellular Biology, Baylor College
ofMedicine,Houston,TX
James N. Petitte Prestage Department of Poultry Science College of Agriculture
andLifeSciencesNorthCarolinaStateUniversityRaleigh,NCUSA
L.PhilipSanford UniversityofIowa,IowaCity,IA
Jorge A. Piedrahita Department of Molecular Biomedical Sciences, North
CarolinaStateUniversity,Raleigh,NC
CarlA.Pinkert Department of Biological Sciences, College ofArts andSciences,
TheUniversityofAlabama,Tuscaloosa,AL
Wendy K. Pogozelski Department of Chemistry, State University of New York at
Geneseo,Geneseo,NY
H. Greg Polites Sanofi R1D Tucson, Sanofi Tucson Research Center, Oro
Valley,AZ
Edmund B. Rucker III Department of Biology, University of Kentucky,
Lexington,KY
Marina Sansinena Embryo Biotechnology Laboratory, Department of Animal
Science,LouisianaStateUniversity,BatonRouge,LA
Angelika Schnieke Livestock Biotechnology, Technische Universita¨t Mu¨nchen,
Freising,Germany
Kumiko Takeda National Agricultural and Food Research Organization, NARO
InstituteofLivestockandGrasslandScience,Tsukuba,Japan
James A. Thomson Plant Gene Expression Center, USDA-University of California,
Berkeley,Albany,CA
Ian A. Trounce Center for Eye Research Australia, University of Melbourne,
Department of Ophthalmology, Royal Victorian Eye and Ear Hospital, East
Melbourne,Australia
xvi ListofContributors
Yukio Tsunoda Laboratory of Animal Reproduction, College of Agriculture,
KinkiUniversity,Nakamachi,Nara,Japan
Cristina Vicente-Garc´ıa National Centre for Biotechnology (CNB-CSIC),
DepartmentofMolecularandCellularBiology,Madrid,Spain
Kevin D. Wells Division of Animal Sciences, National Swine Resource and
ResearchCenter,UniversityofMissouri,Columbia,MO
Richard N. Winn Warnell School of Forest Resources, University of Georgia,
Athens,GA
CurtisR.Youngs DepartmentofAnimalScience,IowaStateUniversity,Ames,IA
Preface
In discussions regarding the third edition of “Transgenic Animal Technology:
A Laboratory Handbook,” we wrestled with the changing tide of technologies and a
revision of the title for 2014. It has, after all, been over two decades since the origi-
naltitlewasestablished.Wastransgenicnowalimitingterm?Weretheembryologi-
cal, animal husbandry, reproductive biology, and molecular techniques something
that should be highlighted in some bolder fashion? Yet it remained true that
transgenic animal technologies and the ability to introduce and modify functional
genes in animal models continue to represent powerful, dynamic, and evolving tools
for dissecting complex biological processes. The questions to be addressed span the
scientific spectrum from biomedical and biological applications to production
agriculture. And yes, as transgenic methodologies continue to evolve, they have dra-
matically influencedacrosssection ofdisciplinesandarerecognizedasinstrumental
inexpandingourunderstandingofgeneexpression,regulation,andfunction.
There are many general reviews on the topic of animal transgenesis and genetic
engineering that are indeed very useful and timely. However, aside from the man-
uals devoted to mouse embryology, a single text illustrating the methodologies
employed by leading laboratories in their respective disciplines had not previously
been compiled priortothefirsteditionofthistext.Thisthirdeditioncovers techni-
cal aspects of gene transfer in animals—from molecular methods to whole animal
considerations across a host of species. Consequently, we kept the title and focus
for this handbook, and it is envisioned as a bridge for researchers and a tool to
facilitate training of studentsand techniciansinthe development and use ofnumer-
oustransgenicanimal modelsystems.
Clearly, much has changed from a technological perspective since the first two
editions in 1994 and 2002. With this in mind, I would like to acknowledge all of
the contributing authors both past and present, as well as those individuals in my
laboratory who have assisted over the course of these three editions. In preparation
of the three editions, a number of colleagues have graciously provided assistance
in reviewing specific chapters and in some cases providing additional data for
consideration prior to publication, for which we are all most grateful. I would also
like to acknowledge all of my mentors, colleagues, and those who came through
my laboratory over the years. Lastly, I am appreciative of the consideration
and help provided by Halima Williams, Radhakrishnan Lakshmanan and their
colleaguesatElsevierforfacilitatingpublicationofthisthirdedition.
CarlA.Pinkert
Tuscaloosa,Alabama
1
Introduction to Transgenic Animal
Technology
Carl A. Pinkert
DepartmentofBiologicalSciences,CollegeofArtsandSciences,TheUniversity
ofAlabama,Tuscaloosa,AL
I. Introduction
The last three decades witnessed a rapid advance of the application of genetic
engineeringtechniquesforincreasinglycomplexorganisms,fromsingle-cellmicrobial
and eukaryotic culture systems to multicellular whole-animal systems. The whole
animal is generally recognized as an essential tool for biomedical and biological
research,aswellasforpharmaceuticaldevelopmentandtoxicological/safetyscreening
technologies. Moreover, an understanding of the developmental and tissue-specific
regulationofgeneexpressionisachievedonlythroughinvivowhole-animalstudies.
Today, particularly with gene editing technologies on the rise, transgenic animals
(andanimalbiotechnologies)continuetoembodyoneofthemostpotentandexciting
researchtoolsinthebiologicalsciences.Transgenicanimalsrepresentuniquemodels
thatarecustomtailoredtoaddress specificbiologicalquestions.Hence,theabilityto
introduce functional genes into animals provides a very powerful tool for dissecting
complex biological processes and systems. Gene transfer is of particular value in
those animal species where long life cycles reduce the value of classical breeding
practices for rapid genetic modification. Foridentificationofinterestingnewmodels,
geneticscreeningandcharacterizationofchancemutationsremainalongandarduous
task. Furthermore,classicalgenetic monitoringcannotadequatelyengineera specific
genetictraitinadirectedfashion.
II. Historical Background
In the early 1980s, only a handful of laboratories possessed the technology neces-
sary to produce transgenic animals. With this in mind, this text is envisioned as
a bridge to the development of various transgenic animal models. Hopefully,
through the first two editions the curiosity and interests of researchers in diverse
research fields were influenced productively. The gene transfer technology that
is currently utilized across vertebrate species was pioneered using mouse and
domestic animal models. Today, the mouse continues to serve as a starting point
TransgenicAnimalTechnology.DOI:http://dx.doi.org/10.1016/B978-0-12-410490-7.00001-3
©2014ElsevierInc.Allrightsreserved.
4 TransgenicAnimalTechnology
for implementing a variety of gene transfer procedures and is the standard for
optimizing experimental efficiencies for many species. Inherent species differ-
ences are frequently discounted by researchers who are planning studies with a
more applicable species model. However, when one attempts to compare experi-
mental results generated in mice to those obtained in other species, not surpris-
ingly many differences become readily apparent. Therefore, an objective of this
textwillbetoaddresstheadaptationofrelevantprotocols.
When initiating work related to gene transfer, it is important to look at the rapid
advancement of a technology that is still primitive by many standards. From an
historical perspective, one readily contemplates potential technologies and methods
that lie just ahead. Whereas modern recombinant DNA techniques are of primary
importance, the techniques of early mammalian embryologists were crucial to the
development of gene transfer technology. While we can look at well over three
decades of transgenic animal production, the preliminary experiments leading to this
text go back millennia to the first efforts to artificially regulate or synchronize
embryo development. Amazingly, it has been more than a century since the first
successful embryo transfer experiments, dating back to the efforts first published
in the 1880s and to Heape’s success in 1891 (Heape, 1891). By the time the studies
by Hammond were reported in the late 1940s, culture systems were developed that
sustained ova throughseveral cleavagedivisions.Suchmethods provideda means to
systematicallyinvestigateanddevelopproceduresforavarietyofeggmanipulations.
These early studies led to experiments that ranged from mixing of mouse embryos
andproductionofchimericanimals,tothetransferofinnercellmasscellsandterato-
carcinomacells,tonucleartransferandthefirstinjectionsofnucleicacidsintodevel-
opingova.Withouttheabilitytocultureormaintainovainvitro,suchmanipulations
ortherequisiteinsightswouldnotbepossible(BrinsterandPalmiter,1986).
Gurdon (1977) transferred mRNA and DNA into Xenopus eggs and observed
thatthetransferrednucleicacidscouldfunctioninanappropriatemanner.Thiswas
followed by a report by Brinster et al. (1980) of similar studies in a mammalian
system, using fertilized mouse ova in initial experiments. Here, using rabbit globin
mRNA,anappropriatetranslationalproductwasobtained.
Major turning points in science continue to accelerate at an incredible pace.
The technology available in 1994 had developed considerably and, as predicted,
a number of areas from both the first and second editions of this text are clearly
antiquated or obsolete today. It is amazing to look back at the major events related
to genetic engineering of animals and how our ability to manipulate both the
nuclearandmitochondrialgenomeshascomesofar.
The production of transgenic mice has been hailed as a seminal event in the
development of animal biotechnology. In reviewing the early events leading to
thefirstgeneticallyengineeredmice,itisfascinatingtonotethattheentireproce-
dure for DNA microinjection was described nearly 50 years ago. While some
progress seems extremely rapid, it is still difficult to believe that, following the
first published report of a microinjection method in 1966 (Lin, 1966; Figures 1.1
and 1.2), it would be another 15 years before transgenic animals were
created. The pioneering laboratories that reported success at gene transfer would