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The Promised Land or Fatal Attraction? A Practical Overview of the
Present and Future of Genetically Engineered Mice
APS Workshop
Donald E. Kohan
C.D. Sigmund, A.A. Mills, A. Nagy and W.C. Skarnes
Genetically engineered mice are important tools in studying development,
physiology, pharmacology, microbiology, immunology, biochemistry, molecular
biology and disease processes. Recent discoveries in hypertension,
diabetes, neural development, cancer, angiogenesis and other areas could
only have been made using genetically engineered mice. The techniques
employed in these mouse models are increasingly diverse and complex.
Improved transgene expression, inducible transgene activation, cell-specific
gene targeting, and mutagenesis of the mouse genome have created
possibilities for understanding normal and pathologic processes heretofore
impossible. With the addition of these valuable tools in the researcher's
armamentarium, several problems have arisen. Many may be unaware of the
possibilities. For others, the potentially bewildering array of techniques
is intimidating. Conversely, the relative novice, attracted by the power of
these tools, may have unrealistic expectations, unaware of the pitfalls and
complications. Even for those not considering using these techniques
themselves, it is important to understand their appropriate application.
As genetically engineered mice gain increasingly popularity and as
powerful new techniques are introduced, it is important that scientists
understand what these techniques are and how they can be successfully
employed. Equally as important, scientists must have a reality check - what
can go wrong and how much time and effort is required. Thus, each speaker
will give a brief overview of the technique in their area of expertise,
discuss an example of its successful use, describe problems and pitfalls,
and close with a figure illustrating the time, effort and cost involved in
their project. A short but relevant bibliography and list of potential
contacts will be placed on the screen at the end of the session. The first
speaker will be Edward Leiter from Jackson Labs who will introduce the
critical concept of considering the effect of genetic background on
phenotype - an area often overlooked. He will relate this to his
experiences studying diabetic mouse models. Curt Sigmund at the University
of Iowa will discuss new techniques for improving reliability of transgene
expression in traditional transgenic mouse models, including BAC clones and
insulator elements. He will draw on his experiences in studying the
renin-angiotensin system. Third, Alea Mills from Cold Spring Harbor Labs
will review inducible gene systems, including the newly described lac operon
system. Andras Nagy from Toronto will review the Cre-lox system, which he
has extensively used in developmental studies. Lastly, Bill Skarnes from UC
Berkeley will discuss the tantalizing prospect of developing libraries of
mice that contain mutations in every gene, focusing on gene trap mutagenesis
and studies on mouse development.
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