Page 68 - Mouse Molecular Genetics

Full Abstracts
Program number is above title. Author in bold is the presenter.
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Laboratory of Integrative Systems Physiology, School of Life Sciences, EPFL, Lausanne, Switzerland; 2) Phenotyping Unit,
Center of PhenoGenomics, School of Life Sciences, EPFL, Lausanne, Switzerland; 3) Department of Anatomy and
Neurobiology, University of Tennessee, Memphis, USA.
Chronic multifactorial diseases, such as type 2 diabetes and obesity, result from the interaction of genes and environmental
factors. In order to better understand this interaction, a mouse genetic reference population allowing control of both genetic and
environmental conditions was used in a pipeline of standardized metabolic tests. A panel of 42 BXD recombinant inbred mouse
lines, descending from C57BL/6J and DBA2/J strains, was used to identify quantitative trait loci (QTL) and gene networks that
modulate metabolic activity. This characterization included exercise endurance, adaptive thermogenesis by means of resistance to
a cold stress, and a glucose tolerance test in a diet-induced obesity paradigm with chow diet (CD) groups versus high-fat diet
(
HFD) groups over 29 weeks. Preliminary results showed a body weight increase during the diet treatment ranging from 16% to
45%
in the CD groups versus 45% to 110% in the HFD groups. Similarly, we found significant differences in the body weight
loss after two weeks of voluntary exercise, with a variation range of -1% to 12% in the CD groups versus 1% to 23% in the HFD
groups. These results reinforce the heterogeneity in the VO2 max, the cold resistance and the glucose tolerance that could be
observed between lines and groups. After completion of the same phenotyping pipeline on about 50 BXD lines, the broad data set
generated with this method will enable QTL mapping strategies through the GeneNetwork resource (www.genenetwork.org). We
presume that the outcome of this work will provide a better understanding of the metabolic syndrome with the identification of
signaling pathways and network regulations. These results will initiate new strategies for diagnosis, prevention and therapy
complex diseases associated with aging, such as obesity and type 2 diabetes.
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The European Mouse Mutant Archive - EMMA. Sabine Fessele
6
,
Glauco Tocchini-Valentini
1
,
Yann Hérault
2,9
,
Steve
Brown
3
,
Urban Lendahl
4
,
Jocelyne Demengeot
5
,
Martin Hrabé de Angelis
6
,
Paul Flicek
7
,
Ramiro Ramirez-Solis
8
,
Lluís
Montoliu
10
,
George Kollias
11
,
Radislav Sedlacek
12
,
Raija Soininen
13
,
Thomas Rülicke
14
. 1)
CNR-Monterotondo, CNR Campus
"
A. Buzzati-Traverso", Monterotondo, Italy (core structure); 2) CNRS - Centre de Distribution, de Typage et d'Archivage Animal
(
CDTA), Orléans, France; 3) Medical Research Council, MRC-Harwell, Harwell, UK; 4) Karolinska Institutet, Department of
Cell and Molecular Biology (KI-CMB), Stockholm, Sweden; 5) Fundaçao Calouste Gulbenkian, Instituto Gulbenkian de Ciencia
(
FCG-IGC), Oeiras, Portugal; 6) Helmholtz Zentrum München, Institute of Experimental Genetics (HMGU-IEG), Neuherberg,
Germany; 7) European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, UK; 8)
Genome Research Limited, Wellcome Trust Sanger Institute (WTSI), Hinxton, UK; 9) GIE-Centre Européen de Recherche en
Biologie et en Médecine, Institut Clinique de la Souris (GIE-CERBM-ICS), Illkirch, France; 10) Consejo Superior de
Investigaciones Scientíficas, Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain; 11) B.S.R.C. Alexander Fleming,
Vari/Athens, Greece; 12) Institute of Molecular Genetics (IMG), Prague, Czech Republic; 13) University of Oulu - Biocenter
Oulu, Oulu, Finland; 14) University of Veterinary Medicine - Biomodels Austria (BIAT), Vienna, Austria.
The European Mouse Mutant Archive (EMMA) offers the worldwide scientific community a free archiving service for its
mutant mouse lines and access to a wide range of disease models and other research tools. A full description of these services can
be viewed on the EMMA website at
At present EMMA holds more than 2700 mouse strains,
corresponding to transgenic mice, induced mutants, gene-traps, knock-ins, knock-outs and also including targeted alleles from
Deltagen, Lexicon and strains produced from the EUCOMM ES cell resource. The EMMA network is comprised of 14 partners
from 11 different countries who operate as the primary mouse repository in Europe. EMMA is funded by the partner institutions,
national research programmes and by the European Commission's FP7 Capacities Specific Programme. EMMA's primary
objectives are to establish and manage a unified repository for maintaining mouse mutations and to make them available to the
scientific community. In addition to these core services, the consortium can generate germ-free (axenic) mice for its customers
and also hosts cryopreservation courses, to promote the use and dissemination of frozen embryos and spermatozoa.
Dissemination of knowledge is further fostered by a dedicated resource database (Wilkinson et al. Nucleic Acids Res. 2010,
38:
D570-6). EMMAs technology development programme focuses on improving sperm cryopreservation methods and the
implementation of laser-assisted IVF and ICSI protocols. All applications for archiving and requests for mutant mouse strains are
submitted through the EMMA website. Mouse strains submitted for archiving are evaluated by EMMA's external scientific
committee. Once approval has been granted depositors are asked to send mice of breeding age to one of the EMMA partners for
embryo or spermatozoa cryopreservation. Strains held under the EMMA umbrella can be provided as frozen materials or re-
derived and shipped as live mice depending on the customer's needs. However, certain strains that are in high demand are
maintained as breeding colonies to facilitate their rapid delivery. All animals supplied by EMMA are classified as SPF in
accordance with the FELASA recommendations. EMMA is a founding member of FIMRe (International Federation of Mouse
Resources) and actively cooperates with other leading repositories like The Jackson Laboratory and the MMRRC in the US and
BRC RIKEN from Japan.
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Occult clonal expansion as a mechanism of intestinal tumor initiation and prevention.
Jared Michael Fischer
1
,
Darryl
Shibata
2
,
Michael Liskay
1
. 1)
Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR; 2)
Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA.
The prevailing dogma of solid tumor progression is that cancer results from the stepwise accumulation of multiple mutations
beginning within a single cell. However, determining how and when driver mutations occur is difficult when examining tumors