In which of the following scenarios could you be sure to obtain a mouse that is homozygous for the transgene?

• A. Mate a chimera with a wild-type mouse.
• B. Mate two hemizygous parents.
• C. Mate two homozygous parents.
• D. It is not possible to know in advance if the offspring will be homozygous.

Answer: (C)

To guarantee that offspring are homozygous for a transgene, both parents must carry two copies of that transgene. When each parent is homozygous, every gamete contains the transgene allele, so fertilization combines two transgene alleles and all offspring end up with two copies—homozygous for the transgene.

If you cross a chimera with a wild-type, you can’t be sure. a chimera has cells with different genotypes, and its germ cells may or may not carry the transgene, leading to unpredictable inheritance. Crossing two hemizygous parents (one copy each) can yield some homozygous offspring, but not all, and you cannot guarantee homozygosity. The idea that you can’t know in advance is incorrect here because a cross between two individuals that are homozygous for the transgene will always produce offspring that are homozygous.