LETHALITY

The first issue is whether overexpression of the transgene is lethal. This problem is
most acute when the transgene is generally overexpressed throughout development.
Lethality may be embryonic or postnatal. Demonstrating embryonic lethality entails
first genotyping progeny of a transgenic mating. The absence of transgenic mice after
screening a significant number of pups strongly suggests embryonic lethality. There
may also be a correlation between transgene dosage and lethality: homozygosity for
the transgene may be a lethal condition, whereas heterozygosity is not. If lethality is
encountered, sometimes simply screening a sufficiently large number of transgenics
will identify viable animals. Presumably such animals are viable because they express the
transgene at lower levels. Another approach is to try a different mouse strain. Outbred
and hybrid strains often reduce the severity of a transgenic phenotype.