FIGURE 1 | Mating scheme of ENU-mutagenesis protocols in the mouse.

From the following article:

Trends in large-scale mouse mutagenesis: from genetics to functional genomics

Yoichi Gondo

Nature Reviews Genetics 9, 803-810 (October 2008)


Trends in large-scale mouse mutagenesis: from genetics to functional genomics

Genome-wide dominant and recessive protocols for phenotype-driven mutagenesis screens. In both screening strategies, N-ethyl-N-nitrosourea (ENU) is administered to generation 0 (G0) males; the crucial step is to detect a mutant phenotype in the mice, indicated by blue rectangles. a | In the dominant-mutation screening scheme, G1 mice are subjected to a series of phenotypic tests. Any G1 animal that has a phenotypic anomaly is a mutant candidate, and is mated to produce G2 mice. When the candidate G1 has a heritable mutation, it is expected to segregate in a 1:1 ratio in the G2 progeny. Mutant animals are indicated by an orange coat and a red cross on the chromosome. When the G0 parental strains are different to each other, a G1 candidate can be mated to the G0 maternal strain to produce G2 backcross progeny. In this case, segregation of the mutant phenotype and of genetic markers, such as SNPs, gives direct genetic linkage information for mapping the identified mutation. b | In recessive-mutation screening, mutant phenotypes are only recognized in the G3 population. Each G1 mouse is expected to carry approx30 recessive mutations (Supplementary information 1 (box)); in this mating scheme, therefore, half of the 30 mutations in any G1 animal are transmitted to the G2. These mutations then become homozygous in a Mendelian 3:1 ratio in G3 mice; alternatively, any G3 mouse might carry approx4 recessive homozygous mutations (Supplementary information 1 (box)). In the recessive-mutation screening scheme the parents usually come from the same strain: if different parental G0 strains were used, the recessive traits in the parental strains would also co-segregate in G3, making the G3 phenotype data complicated to interpret.

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