The modifier of Min 2 (Mom2) locus: Embryonic lethality of a mutation in the Atp5a1 gene suggests a novel mechanism of polyp suppression

The cis–trans test reveals that the Mom2^R mutation functions only when in cis with the Apc^Min mutation. Two crosses were established to test whether Mom2^R could function in trans as well as in cis. Three mating cages of DBA.B6 Mom2^R/+ × DBA.B6 Apc^Min/+ mice produced progeny that carried only the Apc^Min mutation on chromosome 18 (A) or progeny that carried the Apc^Min mutation on one chromosome 18 homolog and the Mom2^R mutation on the other chromosome 18 homolog (C, in trans). Three mating cages of DBA/2J × DBA.B6 Apc^Min/+, Mom2^R/+ mice produced progeny that carried both the Apc^Min and Mom2^R mutations on the same chromosome 18 homolog (B, in cis). All parents of these progeny were at the N9–N12 backcross generations. The chromosomes show the positions of the Apc and Mom2 alleles on chromosome 18 homologs. Below the chromosomes is shown the average number of polyps ± standard deviation. Statistical analyses showed that there is no significant difference in polyp numbers between the control group carrying only the Apc^Min allele and the group that has Apc^Min and Mom2^R in trans. (A vs. C, P > 0.5). In contrast, the only progeny that show highly significant differences with decreased polyp numbers is the Apc^Min group that has Mom2^R in cis (B vs. A, P < 0.0001; B vs. C, P < 0.0001).