CRISPR technology of genome editing helps to manipulate the offspring sex ratio in mice

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Abstract

Development of technologies for producing mainly single-sex progeny is urgently needed for many areas of agriculture and laboratory research that require animals of predominantly one sex. Such technologies would reduce economic costs and address ethical concerns about culling animals of undesired sex. For some species with external fertilization, it is possible to manipulate the offspring sex ratios by changing the temperature or acidity of the environment where the fertilization occurs. However, these methods are not suitable for animals in which sex is determined by a set of sex chromosomes, such as mammals. In this case, breeding systems using genome editing technologies, such as CRISPR-Cas9, can help. This review describes the results of three recent studies on laboratory mice that present different approaches to producing male-only and female-only litters.

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About the authors

A. Yu. Kulibin

Koltzov Institute of Developmental Biology of the Russian Academy of Sciences

Author for correspondence.
Email: Kulibin.A.BKRJ@gmail.com
Russian Federation, Moscow, 119334, ul. Vavilova 26

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2. Fig. 1. Scheme of the experiment to obtain offspring from females only, based on the work (Yosef et al., 2019).

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3. Fig. 2. Schemes for obtaining offspring from only females (A) and only males (B) according to the article (Douglas et al., 2021).

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4. Fig. 3. Scheme of sperm selection for sexual characteristics to obtain all-female mouse litters according to (Yosef et al., 2024). All cells of the transgenic males, including early germ cells, contain a Y chromosome and, in the absence of tetracycline in the drinking water, express a genetic construct that suppresses the expression of the Spem1 gene (blue rectangle). Spem1 is expressed only in haploid germ cells formed as a result of meiotic divisions, a special type of division characteristic only of developing male and female germ cells, leading to a reduction in the number of chromosomes by half and the formation of haploid gametes. In some haploid gametes containing the X chromosome (top), the Spem1 gene is active (green rectangle), and in those containing the Y chromosome (bottom), it is blocked (red rectangle). As a result, X-containing gametes develop normally, while Y-containing gametes either die or become abnormal.

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