Embryonic lethality in homozygous human Her-2 transgenic mice due to disruption of the Pds5b gene. Disruption of the Pds5b gene in B6.Cg-Tg(Wap-ERBB2)229Wzw/J transgenic mice

While heterozygous Wap-ERBB2 mice appear to develop in a similar manner to wild type mice (Her2-/-), it has proven difficult to generate homozygous Her2+/+ mice, potentially due to embryonic lethality. In this study, we performed whole genome sequencing to determine if the integration site of the Her2 transgene was responsible for this lethality. Indeed, we report that the Her2 transgene had integrated into the Pds5b (precocious dissociation of sisters) gene on chromosome 5, as a 162 copy concatemer. Furthermore, our findings demonstrate that Her2+/+ mice, similar to Pds5b-/- mice, are embryonic lethal and confirm the necessity for Pds5b in embryonic development.