Gene-editing used to create single sex mice litters



The genetically modified cells are referred to as the black coat of the mouse. These animals are bred to produce offspring which are genetically modified. The institute is named after Francis Crick.

The Francis Crick Institute and University of Kent have collaborated to create female and male-only mice litters.

This proof of principle study shows how technology can be used to improve animal welfare in scientific research.

There is a need for either male or female animals in scientific research and farming. Animals of the sex being studied are required for laboratory research into male or female reproduction. Female animals are required for egg production and dairy herds in farming. It is common for animals of the un required sex to be culled after birth.

The researchers' new method uses a two-part genetic system to inactivate embryos shortly after fertilisation, allowing only the desired sex to develop. The sex of offspring could be controlled using a genetically-based method.

The embryo selection is based on the fact that there are two parts to the CRISPR-Cas9 that can be used to modify the genome. The team placed one element of the system on the father's X or Y chromosomes, meaning that it will only be passed on to female or male embryos. The mother contributes the other element, which is passed on to all the embryos.

The Top1 gene is essential to DNA replication and repair. When an embryo formed from a sperm and egg, each containing one half of the gene-editing tool, it was not able to develop beyond a very early stage of around 16 to 32 cells.

The researchers were able to control the sex of a litter using this method. To produce a male-only litter, the researchers edited the father's X and Y chromosomes, meaning that only females inherit the deleterious mutations.

The method did not lead to a 50% decrease in the number of offspring produced, rather the litter sizes were between 61% and 72% of the control litters. The researchers think that mice produce more eggs than required during each ovarian cycle, allowing for a portion of them to be lost during early development without reducing litter size. In situations where one sex is needed, fewer breeding animals will be required in order to produce the same number of offspring.

The results may be applicable to other animals as the Top1 gene is well-congruous across mammals.

Charlotte Douglas is the first author and former PhD student at the Crick. The embryo can't develop beyond the very early cell stages.

We've shown that this process works well in different combinations, and that it can be accomplished with either the guide RNA elements or the Cas9 elements.

The sex-selection of the offspring will be prevented if they are bred with an individual of the opposite sex containing the other half of the genome. This is different to genetic engineering in that it seeks to spread a genetic change widely amongst a population.

There are no harmful effects on the surviving offspring.

James Turner, author and group leader of the Sex Chromosome Biology Laboratory at the Crick, says that the work could have immediate and valuable impact in scientific laboratories, as they've shown how it is safe and effective in mice. There are areas of study where only one is needed. When studying the reproductive system, sex-specific diseases, or certain hormones.

The implications of this work are potentially far-reaching when it comes to improving animal welfare, but should be considered at ethical and regulatory levels.

There would need to be a lot of public discussion and debate before any potential use of agriculture. There is a lot of work to be done on the scientific side. First, there needs to be further research to make sure the particular gene editing toolkits are safe and effective.

There is more information about Douglas, C. et al. Sex-specific litters and single-sex litters can be created with the help of the CRISPR-Cas9 effectors. The Nature Communications will be published in 2021. There is a DOI titled " 10.1038/s41467-021-27227-2".

Nature Communications is a journal.

3 December 2016 was retrieved from thephys.org news about thegene-editing-sex-mice-litters.html.

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