A personal history of the mouse genome

The chapter describes some personal reminiscences of various stages in the growth of knowledge of the mouse genome in the past 50 years. Initially mapping was done by crossing new mutants with linkage testing stocks, a slow and laborious method. In the 1950s major mutagenesis experiments led to spin-offs in terms of new mutants, new knowledge of phenomena including sex determination and X-chromosome inactivation, and further understanding of the t-complex. The 1970s saw the development of recombinant inbred (RI) strains and the use of biochemical variants for mapping. In addition the linkage groups were assigned to chromosomes. Techniques of embryo surgery were developed, leading to work with embryonic stem (ES) cells and hence to the identification of gene functioning by knockouts and transgenesis. Another major advance in the 1970s and 1980s was the beginning of comparative mapping, which is now so important. With the advent of DNA technology, progress in mapping increased considerably. Progress became even faster with the use of interspecific backcrosses and with the development of microsatellite markers. The completion of the mouse DNA sequence is now imminent, opening fascinating prospects for the analysis of gene function.