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Gene Targeting: A Practical Approach

Article  in  Journal of Medical Genetics · October 1994


DOI: 10.1136/jmg.31.10.821-a · Source: PubMed Central

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JMed Genet 1994;31:821-822 821

central nervous system and experimental sure that differentiation does not occur before
BOOK REVIEWS therapies for brain tumours.
Although this book is a brave attempt to
reimplantation, make a useful inclusion. De-
tailed protocols include those needed for the
provide a definitive review of its subject, it is production and maintenance of feeder cells,
a little disappointing because of the lack of even the density at which to plate cells in
progress thus far in the subjects addressed. It culture to ensure successful growth. Elec-
If you wish to order or require further in- is, though, well written and in places quite troporation, screening for homologous re-
formation regarding the titles reviewed here, stimulating. A second edition incorporating combination events, DNA preparations, and
please write to or telephone the BMJ Book- the most up to date advances in, say, three the freezing down of large numbers of lines
shop, PO Box 295, London WC1H 9JR. Tel years time would probably be a very exciting are all covered in practical protocols.
071 383 6244. Fax 071 383 6662. Books are volume. Who should read this book? Ideally Chapter 3 represents a departure from the
supplied post free in the UK and for BFPO they would have a postdoctoral level of sci- use of ES cells: the use of bone marrow stem
addresses. Overseas customers should add entific knowledge and have a particular in- cells for gene targeting. This is not commonly
15% for postage and packing. Payment can terest in nervous system tumours. Thus a used, but warrants a chapter as it may be the
be made by cheque in sterling drawn on a postdoctoral scientist beginning work on a technology of the future: the correction of
UK bank or by credit card (Mastercard, Visa, relevant project or an oncologist or neuro- gene defects in cell lines and the manipulation
or American Express) stating card number, surgeon with some scientific background of tissue explants.
expiry date, and full name. (The price and would probably find a number of chapters to In chapter 4, we come to the beginning of
availability are occasionally subject to revision be worthwhile. I doubt that many people in two chapters on the mouse work needed to
by the Publishers.) Britain would buy a personal copy but it is produce chimeric mice. To most people, this
probably worth larger neuroscience de- is probably the least familiar aspect of this
partments having a copy. area of research. The surgical methods and
animal husbandry are covered in great detail,
Molecular Genetics of Nervous System CHRISTOPHER MITCHELL with photographs to carry you through the
Tumours. Ed Arnold J Levine, Henry H detailed manipulation and reintroduction of
Schmidek. (Pp 426.) New York: Wiley-Liss. blastocysts. In contrast to the preceding chap-
1994. ter, which aims at making chimeras through
the injection ofES cells into blastocysts, chap-
When I agreed to review this book I an- Gene Targeting: A Practical Approach. ter 5 presents a less commonly used technique
ticipated, somewhat naively, that I would re- Ed A L Joyner. Practical Approach Series of ES cell aggregation to form blastocysts.
ceive a rather slender volume. I was rather Editors D Rickwood, B D Hames. (LI19.50.) This has the advantage over the injection
startled when a large tome weighing 1-5 kg Oxford: IRL Press at Oxford University Press. of ES cells in that the mice produced are
arrived. A quick inspection of the contents 1994. completely ES cell derived. This is expected
pages showed not that there had been a sud- to give a completely transgenic animal in
den and vast increase in knowledge about the Gene targeting offers a powerful technique the first generation, rather than relying upon
molecular genetics of nervous system tu- for the study of gene expression and mutation chance germline transmission.
mours, but that the editors had chosen to and models of human genetic disorders cre- The book concludes with a chapter on the
include a fairly wide ranging selection of re- ated with such technology have abounded use of ES cells with enhancer and gene trap
views on nervous system development, on- over the last few years. While most people screens where specialised vectors, frequently
cogenes and growth factors, effective ionising are familiar with the overall theory, the actual carrying a lacZ reporter gene, are inserted
radiation on the central nervous system, and mechanics of ES cell culture, blastocyst ma- randomly and the mice generated studied for
strategies for gene mapping and isolation. nipulation, and mouse work are less well a phenotype and assayed for gene expression.
Together these sections comprise nearly half known, often presented as shortened sum- It contains an exhaustive list of constructs
of the book. The latter half of the book is maries in the materials and methods sections which have been made and published, an
devoted to reviews of cytogenetic analysis of of papers. This has led to the protocols by important starting point for anyone con-
human brain tumours and molecular genetic which successful targeting is achieved being sidering starting out with such a strategy.
analysis of nervous system tumours. The final guarded and passed around by word ofmouth As has become the norm for this series of
sections in the book are devoted to metastatic or fax. To counteract this, this book brings publications, this book lives up to the practical
disease within the nervous system and reviews gene targeting into the open. approach title. For experimental detail the
of experimental brain tumour therapy based We are all aware of the Practical Approach layout is excellent. It very much brings this
on viral vectors or plasmids expressing anti- Series from IRL Press and many laboratories technology into the open, and against the
sense transcripts. are adorned with their familiar cover layout. several other rival publications in this rapidly
Coedited by a scientist and a neurosurgeon, They give practical information to researchers moving area, it stands its ground well.
the book is aimed at both scientific and clin- starting out in a field and provide the basics
ical audiences. Most scientists working on in a solidly practical layout. In Gene Targeting, MARK HIRST
the genetics of human cancers will find that individual chapters from specialist authors
substantial parts of the book deal with subjects are welded to a common theme with detailed
already well known to them. However, those protocols from the maintenance and ma-
of them who are unfamiliar with work on nipulation of ES cell lines through to the
nervous system tumours will find the latter details of animal husbandry and the surgical
half of the book to be of interest. The majority manipulations required to reintroduce blasto- Molecular Genetic Medicine. Volume 3.
of clinicians whether they be oncologists, ra- cysts. Researchers familiar with this area Ed T Friedmann. (Pp 184.) New York: Aca-
diotherapists, or neurosurgeons will probably should not lose heart, as sections in this broad demic Press. 1993.
be unfamiliar with most of the subjects reaching book make it an excellent reference
covered. On balance I would expect this book to recent developments in transgenic tech- As previously discussed in these columns, the
to be read rather more by the clinical than nologies and gene targeting. success of detailed review articles depends on
scientific fratermity. The book opens with a lengthy section on a combination of good timing and originality.
As a Paediatric Oncologist I turned first the molecular biology behind the vectors that The best subjects are often those that require
to the chapters on cytogenetic analysis of can be used for targeting. The theoretical and the drawing together of various disparate
paediatric brain tumours and molecular gen- practical considerations of replacement and threads, rather than simple linear thinking.
etic analysis of medulloblastomas. My pre- insertion targeting vectors and the mo- Unfortunately, this third volume of Molecular
judice that little progress had yet been made in difications needed to maximise targeting fre- Genetic Medicine is probably the least suc-
understanding the genetic basis of paediatric quency are discussed in great detail. The cessful to date, because most ofthe six articles
brain tumours was reinforced. There was little chapter ends with an excellent discussion of fail to meet one or both criteria.
information on genetic mechanisms com- making more subtle mutations including "Hit Two contributions are simply out of date.
pared with the extensive knowledge that has and Run" systems. This is essential reading "Molecular biology of Alzheimer's disease"
been gleaned over the past 10 years for other for those embarking on such projects, and is (Whitehouse, Landreth, and Younkin) fo-
paediatric solid tumours. Review of other suitably placed as the opening chapter. cuses largely on the biology of neurotrophins
chapters indicated much of the same problem. In chapter 2, we get to grips with the and [3 amyloid precursor protein. Although it
The sections that I found most interesting propagation and manipulation of ES cell provides a good, scholarly treatment of these
were those devoted to metastasis within the lines. Photographs of ES cell and colony mor- topics, there are virtually no references of
phology, which is essential to monitor to en- 1992 or 1993 vintage. Thus no mention (or
Downloaded from jmg.bmj.com on January 5, 2012 - Published by group.bmj.com

Gene Targeting: A Practical Approach


Mark Hirst

J Med Genet 1994 31: 821


doi: 10.1136/jmg.31.10.821-a

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