A biochemical specific locus mutation system in mice

Abstract

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.

The mutagenesis moonshot: The propitious beginnings of the environmental mutagenesis and genomics society

“…Although beyond the scope of this review, which covers primarily the antecedents of the EMS, Malling's contributions continued apace after he moved to the National Institute of Environmental Health Sciences in the 1970s. There he and Larry Valcovic developed the mouse biochemical specific-locus test for mammalian germ cells (Malling and Valcovic 1977); and later he and James Burkhart developed one of the first transgenic mouse assays for gene mutation (Malling and Burkhart 1989). Another transgenic mouse assay was developed at the same time in the Netherlands at the TNO (Gossen et al 1989).…”

Remembering Heinrich Malling

“…This assay is based on mutations in seven genes that confer visible phenotypes and used thousands of mice. Heinrich's Biochemical Specific‐Locus Test was based on the electrophoretic detection of mutant proteins, and it could be refined to encompass more loci, known gene products, and efficient detection, while using fewer mice [Valcovic and Malling, ; Malling and Valcovic, ; Johnson and Lewis, ].…”