<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>The manipulation of a specific gene in NOD mice, the
best animal model for insulin-dependent diabetes mellitus
(IDDM), must allow for the precise characterization of the
functional involvement of its encoded molecule in the pathogenesis
of the disease. Although this has been attempted by
the cross-breeding of NOD mice with many gene knockout
mice originally created on the 129 or C57BL/6 strain background,
the interpretation of the resulting phenotype(s) has
often been confusing due to the possibility of a known or
unknown disease susceptibility locus (e.g., <italic>Idd</italic> locus) cosegregating
with the targeted gene from the diabetes-resistant
strain. Therefore, it is important to generate mutant mice
on a pure NOD background by using NOD-derived embryonic
stem (ES) cells. By using the NOD ES cell line established
by Nagafuchi and colleagues in 1999 (<italic>FEBSLett.</italic>, 455,
101–104), the authors reexamined various conditions in the
context of cell culture, DNA transfection, and blastocyst injection,
and achieved a markedly improved transmission
efficiency of these NOD ES cells into the mouse germ line.
These modifications will enable gene targeting on a “pure” NOD background with high efficiency, and contribute to
clarifying the physiological roles of a variety of genes in the
disease course of IDDM.</p>
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Exp Diabesity Res. 2004; 5(3):219-226