As the major task of sequencing the human genome is near completion
and full complement of human genes are catalogued, attention will
be focused on the ultimate goal: to understand the normal
biological functions of these genes, and how alterations lead to
disease states. In this task there is a severe limitation in
working with human material, but the mouse has been adopted as the
favored animal model because of the available genetic resources and
the highly conserved gene conservation linkage organization. In
just of ten years since the first gene-targeting experiments were
p- formed in embryonic stem (ES) cells and mutations transmitted
through the mouse germline, more than a thousand mouse strains have
been created. These achievements have been made possible by
pioneering work that showed that ES cells derived from
preimplantation mouse embryos could be cultured for prolonged
periods without differentiation in culture, and that homologous
rec- bination between targeting constructs and endogenous DNA
occurred at a f- quency sufficient for recombinants to be isolated.
In the next few years the mouse genome will be systematically
altered, and the techniques for achi- ing manipulations are
constantly being streamlined and improved.
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