Detection of biochemical mutants in mice.

Several bioanalytical techniques including electrofocusing, two-dimensional technique comprising electrofocusing and electrophoresis, and chromatography have been evaluated and improved to provide a method for detecting gene mutations in mice. The use of 1 mm gels for both electrofocusing and electrophoresis in the two-dimensional technique resulted in better resolution, shorter separation time, and reduced costs. An electrophoretic apparatus for the second direction electrophoresis has been designed which eliminated cutting of a flat gel into strips prior to electrophoresis. These changes reduced the total time for a two-dimensional separation to 4 h. The scope and application of isoelectric focusing in detecting gene mutations in mice have been improved by the agar contact replica method. This method allows the simultaneous analysis of several genetic loci besides facilitating automation of evaluation, documentation, and storage of zymograms. Preliminary studies on the detection of heritable metabolic disorders of amino acid metabolism in mice show a potential for such studies in estimating mutation rates in mice. Some possible techniques for such studies and their implications are discussed.