# Conplastic FVB/N-mt129S6/SvEvTac mice: A new tool for cancer research

## TL;DR

Researchers created a new mouse strain to study cancer and stem cells, which combines the FVB/N nuclear genome with 129S6 mitochondria.

## Contribution

The study introduces a conplastic mouse strain that enables germline-competent stem cell generation and cancer research in the FVB/N background.

## Key findings

- Cancer incidence was similar between FVB/N and conplastic mice, but cancer grade was higher in the conplastic strain.
- Conplastic mice supported the generation of germline-competent embryonic stem cells, unlike standard FVB/N mice.
- Mitochondrial genome differences did not affect cancer incidence but influenced cancer severity.

## Abstract

FVB/N mice, which are commonly used for cancer studies, have accelerated onset of endometrial cancer following developmental estrogenic chemical exposure. These mice also have a polymorphism in the mitochondrial gene, mt-Atp8, leading to increased production of reactive oxygen species. We hypothesized that this polymorphism contributes to the enhanced endometrial cancer phenotype in FVB/N mice. To test this idea, we generated conplastic FVB/N-mt129S6/SvEvTac mice (FVB/N nuclear genome; 129S6/SvEvTac mitochondria: FVB/N-mt129). The impact of 129S6 versus FVB/N mitochondrial genomes on endometrial cancer development following neonatal exposure to the xenoestrogen, diethylstilbestrol, was tested by comparing the cancer phenotypes of FVB/N mice to FVB/N-mt129 mice. There was no difference in cancer incidence regardless of mitochondria source, but cancer grade was higher in the conplastic strain. Additionally, while the FVB/N genetic background is considered non-permissive for generation of pluripotent mouse embryonic stem cells, blastocysts from the conplastic background readily generated mouse embryonic stem cell clones that supported gene editing in culture and subsequently generated germline competent chimeric founder mice. FVB/N-mt129 mice are a potentially powerful resource for generating germline competent embryonic stem cells with an FVB/N nuclear genome and for studying cancer phenotypes.