A biochemical specific locus mutation system in mice.

Two mouse strains DBA/2J and C57BL/6J are heteromorphic with respect to the electrophoretic mobility of at least 8 enzymes and the beta-hemoglobin chain. The genotype of DBA/2J for these markers is: Es-1, Es-3, Gpd-1, Gpi-1, Id-1, Mod-1, Pmg-1, Dip-1 and Hbb; and of C57B1/6J: Es-1, Es-3, Gpd-1, Gpi-1, Id-1, Mod-1, Pgm-1, Dip-1 and Hbb. Electrophoresis on tissues of interstrain hybrids will show the two parental bands and additional hybrid bands if the enzyme is a polymeric structure. In specific locus mutations which result in loss of activity (deletions, nonsense mutations), the hybrid resembles the non-mutated parent. In the mutation results in a change in electrophoretic mobility, some of the bands on the gel will either run faster or slower compared to the hybrid bands in a normal F1 animal. Fifty DBA/2J males were irradiated with gamma-rays from a Co60 source with two doses of 500 R at 24-h intervals at a dose rate of 95 R/min. After this irradiation the males were sterile for approximately 3 months. After the males regained their fertility, they were continuously mated to C57BL/6 females. Thus far somewhat over 2600 animals have been tested and four new mutations detected, giving a frequency of approximately 1.7 X 10(-4) mutations per locus per generation. The four mutations are: two independent mutations at Hbb, one at Mod-1 and one at Id-1.