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To make null mutant mice, it takes at least about one year from the construction of the targeting vector if there is no delay during the whole procedure from steps such as colony selection of ES cells, chimera production and confirmation of germ line transmission for the mice.
So, if the ES cells which have a null mutation in the genome aggregate with tetraploid embryos, null mutation pups can be produced directly without passing through the chimera selection and germ line transmission steps (Figure 8).