1. the mutated allele had dominant negative effect-most likely 2. gene dosage effect-less likely 3. There is a second random mutation happened, which is closely linked with your targeted locus--very unlikely possible solution: 1.You may try to breed your chimera with different mouse strains. Sometimes mutant phenotypes are affected by genetic background. 2. If you are really desperate, you may try ovarian transplantation.
I think 楼主 need to describe which kind of phenotype he is referring to, some phenotype would actually disappear after several rounds of back cross
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【在 g***y 的大作中提到】 : 1. the mutated allele had dominant negative effect-most likely : 2. gene dosage effect-less likely : 3. There is a second random mutation happened, which is closely linked with : your targeted locus--very unlikely : possible solution: : 1.You may try to breed your chimera with different mouse strains. Sometimes : mutant phenotypes are affected by genetic background. : 2. If you are really desperate, you may try ovarian transplantation.