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5th
EMBL/EMBO Joint Conference 2004 |
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Session I |
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| Use
of the mouse to study human longevity |
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Mario Capecchi,
Professor of Human Genetics, University of Utah,
School of Medicine, Salt Lake City, USA
Gene targeting provides
the means for creating strains of mice with designed
alteration in any chosen genetic locus. This technology
permits the evaluation of the functions of genes
in the intact mammal and the systematic dissection
of the most complex biological processes from embryogenesis
to aging. With virtually complete control over how
a gene's DNA sequence is modified, the investigator
can disrupt the gene in the germline, and as a consequence,
every cell of the mouse carries the disrupted gene,
or the modification can be implemented conditionally,
thereby restricting the function of the gene in
chosen tissues and/or temporal periods of the animal,
including adulthood. Of all of the model organisms,
the mouseŠs genome and physiology is most similar
to ours, so it would appear that this creature is
likely to be the most informative experimental organism
to evaluate the multiple facets that affect the
process of aging and permit evaluation of the genetic
and environmental factors that most significantly
alter the aging process. Is it reasonable to anticipate
that the lifespan of the laboratory mouse can be
significantly changed through genetic manipulations?
Comparisons among the life spans of different mammalian
species of comparable size and physiology suggest
that it should be. For example, the average life
span of the laboratory mouse is approximately two
years. However, the microbat species Myotis lucifugus
readily attains a life expectancy of thirty years.
These two species are nearly identical in size and
have very similar physiological parameters such
as heart rates, blood pressure, body temperatures
and metabolic rates. It is not unreasonable to assume
that such enormous differences in life expectancies
between these two species is determined in part
by genetic differences. We will explore technologies
that use the mouse as a surrogate and may allow
the identification of such genetic determinants. |
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