Embryonic Lethality in Homozygous Human Her-2 Transgenic Mice Due to Disruption of the Pds5b Gene

PloS One
Carmen S M YongMichael H Kershaw

Abstract

The development of antigen-targeted therapeutics is dependent on the preferential expression of tumor-associated antigens (TAA) at targetable levels on the tumor. Tumor-associated antigens can be generated de novo or can arise from altered expression of normal basal proteins, such as the up-regulation of human epidermal growth factor receptor 2 (Her2/ErbB2). To properly assess the development of Her2 therapeutics in an immune tolerant model, we previously generated a transgenic mouse model in which expression of the human Her2 protein was present in both the brain and mammary tissue. This mouse model has facilitated the development of Her2 targeted therapies in a clinically relevant and suitable model. While heterozygous Her2+/- 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 demon...Continue Reading

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Citations

Jun 28, 2019·Frontiers in Genetics·Jorune Balciuniene, Darius Balciunas
Aug 17, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wei-Zen WeiKuang-Chung Wei
Dec 23, 2016·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Ting MoZili Zhang
Dec 15, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Clare Y SlaneyMichael H Kershaw
Sep 4, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Aesha I AliClare Y Slaney

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Datasets Mentioned

BETA
X03363
PRJEB9805

Methods Mentioned

BETA
transgenic
PCR
genotyping

Software Mentioned

Socrates
Bowtie2
IGV viewer
- FREEC
BLAST
Control

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